Phenolic composition,antioxidant and enzyme inhibitory activities of Parkia biglobosa (Jacq.) Benth., Tithonia diversifolia (Hemsl) A. Gray,and Crossopteryx febrifuga (Afzel.) Benth

Medicinal plants from Chad grow under special climatic conditions in between the equatorial forest of Central Africa and the desert of North Africa and are understudied. Three medicinal plants from Chad (T. diversifolia, P. Biglobosa and C. Febrifuga) were evaluated for their phenolic composition, antioxidant and enzyme inhibition activities. The total phenolic composition varied from 203.19 ± 0.58 mg GAE/g DW in the ethyl acetate extract of P. biglobosa, to 56.41 ± 0.89 mg GAE/g DW in the methanol extract of C. febrifuga while the total flavonoid content varied from 51.85 ± 0.91 mg QE/g DW in the methanol extract of P. biglobosa to 08.56 ± 0.25 mg QE/g DW in the methanol extract of C. febrifuga. HPLC-DAD revealed that rutin, gallic acid and protocatechuic acid were the most abundant phenolics in T. diversifolia, P. Biglobosa and C. Febrifuga respectively. The antioxidant activity assayed by five different methods revealed very good activity especially in the DPPH^?, ABTS^?+ and CUPRAC assays where the extracts were more active than the standard compounds used. Good inhibition was exhibited against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with methanol (IC₅₀: 15.63 ± 0.72 µg/mL), ethyl acetate (IC₅₀: 16.20 ± 0.67 µg/mL) extracts of P. biglobosa, and methanol (IC₅₀: 21.53 ± 0.65 µg/mL) and ethyl acetate (IC₅₀: 30.81 ± 0.48 µg/mL) extracts of T. diversifolia showing higher inhibition than galantamine (IC₅₀: 42.20 ± 0.44 µg/mL) against BChE. Equally, good inhibition was shown on α-amylase and α-glucosidase. On the α-glucosidase, the ethyl acetate (IC₅₀ = 12.47 ± 0.61 µg/mL) and methanol extracts (IC₅₀ = 16.51 ± 0.18 µg/mL) of P. biglobosa showed higher activity compared to the standard acarbose (IC₅₀ = 17.35 ± 0.71 µg/mL) and on α-amylase, the ethyl acetate (IC₅₀ = 13.50 ± 0.90 µg/mL) and methanol (IC₅₀ = 18.12 ± 0.33 µg/mL) extracts of P. biglobosa showed higher activity compared to acarbose (IC₅₀ = 23.84 ± 0.25 µg/mL). The results indicate that these plants are good sources of antioxidant phenolics and can be used to manage oxidative stress linked illnesses such as Alzheimer’s disease and diabetes.     

One-pot multicomponent synthesis of novel 3, 4-dihydro-3-methyl-2(1H)-quinazolinone derivatives and their biological evaluation as potential antioxidants,enzyme inhibitors,antimicrobials, cytotoxic and anti-inflammatory agents

A series of novel 3, 4-dihydro-3-methyl-2(1H)-quinazolinone derivatives with substituted amine moieties (1–13) and substituted aldehyde (S) were designed and synthesized by a reflux condensation reaction in the presence of an acid catalyst to get N-Mannich bases. Mannich bases were evaluated pharmacologically for their antioxidant, α-amylase enzyme inhibition, antimicrobial, cell cytotoxicity and anti-inflammatory activities. Most of the compounds exhibited potent activities against these bioassays. Among them, SH1 and SH13 showed potent antioxidant activity against DPPH free radical at IC₅₀ of 9.94 ± 0.16 µg/mL and 11.68 ± 0.32 µg/mL, respectively. SH7, SH10 and SH13 showed significant results in TAC and TRP antioxidant assays, comparable to that of ascorbic acid. SH2 and SH3 showed potent activity in inhibiting α-amylase enzyme at IC₅₀ of 10.17 ± 0.23 µg/mL and 9.48 ± 0.17 µg/mL, respectively, when compared with acarbose (13.52 ± 0.19 µg/mL). SH7 was the most active against gram-positive and gram-negative bacterial strains, SH13 being the most potent against P. aeruginosa by inhibiting its growth up to 80% (MIC = 11.11 µg/mL). SH4, SH5 and SH6 exhibited significant activity against some fungal strains. Among the thirteen synthesized compounds (SH1-SH13), four were screened out based on the results of brine shrimp lethality assay (LD₅₀) and cell cytotoxicity assay (IC₅₀), to determine their anti-cancer potential against Hep-G2 cells. The study was conducted for 24, 48, and 72 h. SH12 showed potent results at IC₅₀ of 6.48 µM at 72 h when compared with cisplatin (2.56 µM). An in vitro nitric oxide (NO) assay was performed to shortlist compounds for in vivo anti-inflammatory assay. Among shortlisted compounds, SH13 exhibited potent anti-inflammatory activity by decreasing the paw thickness to the maximum compared to the standard, acetylsalicylic acid (ASA).     

Total phenolic and flavonoid contents,antioxidant, antidiabetic and antiplasmodial activities of Garcinia forbesii King: A correlation study

Garcinia forbesii King belongs to Clusiaceae is a source of secondary metabolites especially xanthones with various biological activities. G. forbesii King is also known for its empirical use for malaria and diabetes. This study investigated the total phenolic and flavonoid contents, in vitro antioxidant, antidiabetic and antiplasmodial activities of four extracts attained from the stem bark of G. forbesii King. The total phenolic and flavonoid contents were determined by spectrophotometric methods and antioxidant activity was evaluated by DPPH, ABTS, FRAP assays. In vitro antidiabetic activity was assessed by α-glucosidase and α-amylase assays and antiplasmodial activity was studied against chloroquine sensitive Plasmodium falciparum strain 3D7. The highest value of total phenolic (187.37 ± 0.06 mg GAE/g) and flavonoid (35.97 ± 0.02 mg QE/g) contents were recorded in n-hexane and methanolic extracts. n-Hexane extract showed the highest DPPH activity with IC₅₀ of 8.12 ± 0.02 μg/mL. Ethyl acetate extract exhibited better scavenging ability for ABTS with IC₅₀ of 3.88 ± 0.04 μg/mL. The FRAP assay showed better activity in methanol extract with an inhibition value of 73.68 ± 3.66 µM Fe²⁺/g. The strong inhibition against α-glucosidase and α-amylase were displayed by dichloromethane extract with IC₅₀ of 35.13 ± 2.01 μg/mL and 4.83 ± 0.20 μg/mL. n-Hexane and methanol extracts showed significant antiplasmodial activity with IC₅₀ of 0.23 ± 0.01 μg/mL and 0.73 ± 0.01 μg/mL, respectively. The correlation analysis indicated a positive relationship of total phenolic and flavonoid contents with antiplasmodial activity. The results revealed that n-hexane and methanol extracts could be used as a potential natural antiplasmodial, while dichloromethane extract is a promising natural antidiabetic.     

In vitro evaluation of novel mefenamic acid derivatives as potential α-glucosidase and urease inhibitors: Design,synthesis, in silico and cytotoxic studies

This study aim to synthesize new 1,3,4-oxadiazole derivatives incorporating mefenamic acid as promising α-glucosidase and urease inhibitors, potentially leading to the treatment of postprandial hyperglycemia as well as H. pylori related disorders. In this regards, we have designed a series of Mefenamic acid derivatives. The synthetic compounds were structurally elucidated through ¹H NMR, ¹³C NMR and HR-EIMS analysis. The biological evaluation of these derivatives against α-glucosidase and urease enzyme depicted some novel derivatives with potent inhibition against the said enzymes. All the derivatives exhibited potent inhibition against α-glucosidase enzymes with IC₅₀ ranging from 25.81 ± 1.63–113.61 ± 1.31 µM against standard drug acarbose (IC₅₀ = 375.82 ± 1.76 µM) while with respect to urease these derivatives possessed inhibitory potential varied between IC₅₀ = 8.04 ± 1.01–58.18 ± 1.03 µM against the standard thiourea (IC₅₀ = 21.0 ± 1.76 µM). The cell viability results revealed that all of the derivatives were found least cytotoxic. Furthermore, molecular docking studies of the most potent derivatives identify number of key features involved in binding interactions between potential inhibitors and the enzyme's active site.     

Volatile constituents of Amomum argyrophyllum Ridl. and Amomum dealbatum Roxb. and their antioxidant,tyrosinase inhibitory and cytotoxic activities

The volatile components from fresh rhizomes and leaves of Amomum argyrophyllum Ridl. and Amomum dealbatum Roxb. were performed using HS-SPME and charac-terized by GC–MS. A total of 49, 47, 49, and 34 compounds were identified from the rhizomes and leaves of A. argyrophyllum and A. dealbatum, respectively. The major components were β-pinene, α-pinene, and o-cymene. The rhizome extracts exhibited total phenolic content of 2.9 ± 0.5 and 2.1 ± 0.6 mg gallic acid equivalents. The IC₅₀ values of DPPH and ABTS were 179.8 ± 3.9 µg/mL, 392.9 ± 2.6 µg/mL, 120.3 ± 2.5 µg/mL, and 328.6 ± 3.3 µg/mL, respectively. The FRAP values were 76.5 ± 7.8 and 84.9 ± 4.4 µM ascorbic acid equivalents. The extracts showed weak antibacterial activity and tyrosinase inhibitory activity of 69.0 ± 3.6 and 53.7 ± 7.4 mg kojic acid equivalents. The cytotoxicity effect was assessed with the MTT assay at 200 µg/mL. The extracts showed no toxicity. In addition, the anti-inflammatory properties of extracts were evaluated, and showed potential to inhibit nuclear factor-κB (NF-κB) activity.     

Metabolomic profile and in vitro evaluation of the cytotoxic activity of Asphodelus microcarpus against human malignant melanoma cells A375

Melanoma is a huge worldwide health problem that must be handled more effectively with better therapeutic options. As a result, new treatment drugs are required to treat this condition. The goal of this study was to investigate the cytotoxic activity of the anthraquinone-rich fractions obtained from Asphodelus microcarpus against human melanoma cell A375. On these melanoma cell lines; the cytotoxicity of these fractions had never been studied before. Liquid chromatography linked to mass spectrometry (LC-MS-MS) and Nuclear Magnetic Resonance was used to determine the chemical profiles of these fractions. The cytotoxicity of the fractions studied was determined by measuring cell viability and calculating IC₅₀ values. Both ethyl acetate (EtOAC) and the precipitate fractions (PPT) exhibited selective cytotoxicity on human melanoma A 375 cell line with IC₅₀ values of 83 and 65 µg/mL, respectively. The antiproliferative properties of EtOAc fraction and PPT were supported by a noticeable decrease in cell numbers during the G2/M cell cycle arrest. Our findings suggest that the anthraquinone content of A. microcarpus tubers is responsible for its anti-proliferative and apoptotic properties and that further in vivo investigations should be conducted to establish the viability of using them to treat human melanomas.     

Design,synthesis of new novel quinoxalin-2(1H)-one derivatives incorporating hydrazone,hydrazine, and pyrazole moieties as antimicrobial potential with in-silico ADME and molecular docking simulation

A series of 6-(morpholinosulfonyl)quinoxalin-2(1H)-one based hydrazone, hydrazine, and pyrazole moieties were designed, synthesized, and evaluated for their in vitro antimicrobial activity. All the synthesized quinoxaline derivatives were characterized by IR, NMR (¹H /¹³C), and EI MS. The results displayed good to moderate antimicrobial potential against six bacterial, and two fungal standard strains. Among the tested derivatives, six quinoxalin-2(1H)-one derivatives 4a, 7, 8a, 11b, 13, and 16 exhibited a significant antibacterial activity with MIC values (0.97–62.5 µg/mL), and MBC values (1.94–88.8 µg/mL) compared with Tetracycline (MICs = 15.62–62.5 µg/mL, and MBCs = 18.74–93.75 µg/mL), and Amphotericin B (MICs = 12.49–88.8 µg/mL, and MFC = 34.62–65.62 µg/mL). In addition, according to CLSI standards, the most active quinoxalin-2(1H)-one derivatives demonstrated bactericidal and fungicidal behavior. Moreover, the most active quinoxaline derivatives showed a considerable antibacterial activity with bactericidal potential against multi-drug resistance bacteria (MDRB) strains with MIC values ranged between (1.95–15.62 µg/mL), and MBC values (3.31–31.25 µg/mL) near to standard Norfloxacin (MIC = 0.78–3.13 µg/mL, and MBC = 1.4–5.32 µg/mL. Further, in vitro S. aureus DNA gyrase inhibition activity were evaluated for the promising derivatives and displayed potency with IC₅₀ values (10.93 ± 1.81–26.18 ± 1.22 µM) compared with Ciprofloxacin (26.31 ± 1.64 µM). Interestingly, these derivatives revealed as good immunomodulatory agents by a percentage ranging between 82.8 ± 0.37 and 142.4 ± 0.98 %. Finally, some in silico ADME, toxicity prediction, and molecular docking simulation were performed and showed a promising safety profile with good binding mode.     

Bioprospecting Dodonaea viscosa Jacq.; a traditional medicinal plant for antioxidant,cytotoxic, antidiabetic and antimicrobial potential

Purpose of studyDodonaea viscosa Jacq. is an ethnomedicinal plant that has been extensively used for the treatment of gout, rheumatism and pain. Current study was undertaken to mine its antioxidant, antimicrobial, cytotoxic and antidiabetic potential. Chromogenic assays were employed to establish plant’s multimode antioxidant profile whereas HPLC fingerprinting was performed to quantify polyphenols. Standard brine shrimp lethality, MTT and SRB assays proved its cytotoxicity potential.ResultsAmong all the extracts (flower, leaf, stem and root), maximum extract recovery (22% w/w), gallic acid equivalent total phenolic content (20.11 ± 0.11 ug GAE/mg DW), ascorbic acid equivalent total antioxidant capacity (22.5 ± 0.07 µg/mg DW) and total reducing power (31.1 ± 1.13 µg/mg DW) were recorded in the distilled water + acetone extract of leaf. The acetone extract of leaf showed maximum quercetin equivalent total flavonoid content (4.78 ± 0.13 µg/mg DW). HPLC-DAD analysis revealed significant amount of rutin, vanillic acid, coumaric acid, ferulic acid, gallic acid, syringic acid, cinnamic acid, gentisic acid, catechin, caffeic acid, apigenin and myricetin in the different plant parts. Maximum scavenging potential was exhibited by methanol + ethyl acetate stem extract (IC₅₀ = 23.8 µg/ml). The highest antibacterial potential was found in flower (85.7%) and root (71.4%) extracts. The ethanol + ethyl acetate (1:1) leaf extract showed noteworthy toxicity against brine shrimps (LC₅₀ = 95.46 µg/ml) while a notable antiproliferative activity against THP-1 (IC₅₀ = 3.4 µg/ml) and Hep G2 (IC₅₀ = 20 µg/ml) cell lines was shown by ethanol + ethyl acetate extracts (1:1) of stem and root, respectively. A moderate inhibition of α-amylase enzyme was observed in all parts of the plant.ConclusionThe results of the present study suggest D. viscosa as a potential source of antioxidant, anticancer and α-amylase inhibitory phytochemicals.     

UPLC-ESI-QTOF-MS phenolic compounds identification and quantification from ethanolic extract of Myrtus communis ‘Variegatha’: In vitro antioxidant and antidiabetic potentials

Global public health is seriously threatened by diabetes and its complications. Although several synthetic drugs are currently employed for managing diabetes, however, the adverse effects associated with their use cannot be underestimated. Thus, the quest for a safe and cost-effective alternative is highly imperative. In the present study, the phenolic contents, antioxidant, antidiabetic, and cytotoxic potentials of 70% ethanolic crude extract of Myrtus communis ‘Variegatha’ were investigated using in vitro biochemical protocols. The total polyphenols content was 116.44 mg GAE/g, flavonols (6.74 mg QE/g), flavanols (2.46 mg CE/g) and the ferric reducing antioxidant power (FRAP) value was 1267.28 µmol AAE/g, 2,2-diphenyl-1-picrylhydrazyl (DPPH) (1165.37 µmol TE/g), and Trolox equivalent antioxidant capacity (TEAC) (775.52 µmol TE/g). High-resolution ultra-performance liquid chromatography coupled with electrospray ionisation/quadrupole-time-of-flight-mass spectrometry (UPLC-ESI-QTOF-MS) was explored to identify the phenolic compounds, most of which were flavonoids. The extract demonstrated a strong α-glucosidase inhibition potential in a concentration-dependent manner with IC₅₀ (3.159 µg/mL), which was higher than epigallocatechin gallate (EGCG) (6.208 µg/mL), a positive control antidiabetic drug. A slight increase in glucose utilization was observed after 24 h of treatment in C3A hepatocytes at 25 μg/mL whereas an increase in glucose uptake was recorded at 25 and 50 μg/mL. The extract exhibited a cytotoxic effect (IC₅₀ 76.85 µg/mL) against C3A hepatocytes at 100 µg/mL, which correlates to the glucose utilization and uptake recorded. The findings from the study show the prospect of M. communis ‘Variegatha’ as a promising source of bioactive compounds that could be used in the development of new anti-diabetic agents, thus, further research into the plant is recommended.     

Bioinspired synthesis of pure massicot phase lead oxide nanoparticles and assessment of their biocompatibility,cytotoxicity and in-vitro biological properties

Green and ecofriendly route for biosynthesis of lead oxide nanoparticles has been successfully demonstrated using aqueous leaf extracts of Sageretia thea (Osbeck.). Biosynthesized PbO (∼27 nm) nanoparticles were extensively characterized using XRD, FTIR, Raman, EDS etc. Morphology was studied through HR-TEM/SEM. As synthesized nanoparticles were investigated for their iv-vitro biological properties. Antibacterial activities revealed enhancement upon modulation by UV in a concentration dependent manner. Pseudomonas aeruginosa was found to be the most resistant strain (MIC = 250 µg/mL and MIC^uv = 31.25 µg/ml). MTT cytotoxicity on leishmania promastigotes and amastigotes revealed significant inhibition as indicated by their IC₅₀ values of 14.7 µg/mL and 11.95 µg/m respectively. Cytotoxicity was also confirmed using brine shrimp lethality (IC₅₀ = 27.7 µg/mL). Bio-compatibility evaluation indicated cytotoxicity to freshly isolated human macrophages (IC₅₀ = 57.1 µg/mL). Insignificant alpha-amylase inhibition and moderate protein kinase inhibition was revealed. Antioxidant activities indicated free radical scavenging activity (58 ± 2.45) at 200 µg/mL. Moderate total reducing power and total antioxidant activity was also indicated. Overall, we conclude lead oxide as a potential candidate for biological applications, however further studies are recommended on their in vitro and in vivo cytotoxicity.     

Synthesis,biological evaluation and molecular docking study of pyrimidine based thiazolidinone derivatives as potential anti-urease and anti-cancer agents

Hybrid analogs containing molecules are always the choice of different synthetic researcher due to their diverse biological applications and significantly more efficient. Heterocyclic being a good inhibitors against varied disease are most commonly used in drug designing and development. The current study also addressed the synthesis of pyrimidine-based thiazolidinone derivatives (1–13) using stepwise processes and their structure was confirmed using various characterization techniques such as ¹HNMR, ¹³CNMR, and HREI-MS. Furthermore, the biological significances of the synthesized scaffolds were also explored and proved to be as anti-urease and anti-cancer moieties. Their inhibitory potentials were determined using the minimum inhibitory concentration (MIC) in the presence of their standard drugs, Thiourea (IC₅₀ = 8.20 ± 0.20 µM) and Tetrandrineb (IC₅₀ = 12.30 ± 0.10 µM) respectively. Structure activity relationship (SAR) was established for all the synthesized scaffolds and compared their inhibitory potentials in which scaffolds 3 (IC₅₀ = 2.30 ± 0.30 and 3.20 ± 0.50 µM), 6 (IC₅₀ = 3.10 ± 0.20 and 6.20 ± 0.10 µM), 7 (IC₅₀ = 3.20 ± 0.20 and 3.80 ± 0.30 µM) and 10 (IC₅₀ = 4.20 ± 0.20 and 5.10 ± 0.30 µM) exhibited the most influential activity. These compounds were subsequently examined using molecular docking experiments, which evaluate the binding interaction of ligands with enzyme active sites.     

Potential enzyme inhibitor triazoles from aliphatic esters: Synthesis,enzyme inhibition and docking studies

Enzyme inhibitors are vital aspects for studying enzymes and are employed as drugs to treat certain disorders, thus implying pivotal role in drug discovery. In the current study, a series of triazole compounds 4(a-o) were synthesised to explore their inhibitory potential against α-glucosidase and urease enzymes. These derivatives with dichlorophenyl substituents were prepared by cyclization of thiosemicarbazides and their structures were confirmed through spectroanalytical techniques. The in vitro biological screening revealed that the compounds 4a, 4b, 4k, 4l, 4m, 4o having IC₅₀ values of 121.09 ± 1.25, 137.22 ± 0.22, 110.4 ± 2.4, 114.79 ± 1.1, 146.72 ± 1.29, 94.21 ± 0.15 [µM] respectively, exhibited good potential α-glucosidase inhibition, in comparison to Acarbose: IC₅₀ 51.23 µM, while the compounds 4a, 4b, 4c, 4k, 4l, having IC₅₀ values of 48.52 ± 0.39, 52.22 ± 1.37, 60.98 ± 0.34, 37.06 ± 0.51, 38.66 ± 1.7 [µM] respectively exhibited good potential for urease inhibition near to standard(Thiourea: IC₅₀ 24.14 [µM]). These in vitro findings were accompanied further by molecular docking simulations, which revealed significant binding interactions of the synthesized derivatives within the active sites of the enzymes.     

Angiotensin I-Converting Enzyme Inhibitory Proteins and Peptides from the Rhizomes of Zingiberaceae Plants

Ammonium sulphate cut protein extracts, and their pepsin hydrolysates, from the rhizomes of 15 plants in the Zingiberaceae family were screened for their in vitro angiotensin I-converting enzyme inhibitory (ACEI) activity. The protein extract from Zingiber ottensii had the highest ACEI activity (IC₅₀ of 7.30 × 10⁻⁷ mg protein/mL) and was enriched for by SP Sepharose chromatography with five NaCl step gradients 0, 0.25, 0.50, 0.75 and 1 M NaCl collecting the corresponding five fractions. The highest ACEI activity was found in the F75 fraction, which appeared to contain a single 20.7-kDa protein, suggesting enrichment to or near to homogeneity. The ACEI activity of the F75 fraction was moderately thermostable (−20–60 °C), showed >80% activity across a broad pH range of 4–12 (optimal at pH 4–5) and appeared as a competitive inhibitor of ACE (K _i of 9.1 × 10⁻⁵ mg protein/mL). For the pepsin hydrolysates, that from Zingiber cassumunar revealed the highest ACEI activity (IC₅₀ of 0.38 ± 0.012 mg/mL), was enriched to a single active hexapeptide by RP-HPLC with a strong ACEI activity (IC₅₀ of 0.011 ± 0.012 mg/mL) and acted as a competitive inhibitor of ACE (K _i of 1.25 × 10⁻⁶ mg protein/mL).     

Design,synthesis, biological evaluation and in silico studies of novel 1,2,3-triazole linked benzoxazine-2,4-dione conjugates as potent antimicrobial,antioxidant and anti-inflammatory agents

In an attempt to rationalize the search for new potential anti-inflammatory and anti-infection agents, a new series of 1,4-and 1,5-disubstituted 1,2,3-triazoles linked benzoxazine conjugates have been synthesized via “Click Chemistry” reaction, were designed, synthesized and characterized by means of spectral and elemental data. The newly synthesized compounds have been assessed for their antimicrobial, antioxidant and anti-inflammatory potential. Results revealed that all synthesized compounds display superior activities to the standard drug against different bacterial strains especially S. aureus, M. luteus, and P. aeruginosa, with good to moderate activity towards the tested E. coli bacteria, in respect to the commercial antibiotic, tetracycline. Moreover, the antifungal activity was screened against C. albicans and C. krusei yeasts and results demonstrate potent activity as compared to the standard drug, ampicillin. The antioxidant activity was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging assays, whose results indicate that analogues 4a (IC₅₀ 1.88 ± 0.07 µM and 2.17 ± 0.02) followed by 4b (IC₅₀ 2.19 ± 0.09 µM and 2.38 ± 0.43 µM), 4d (IC₅₀ 2.30 ± 0.01 µM and 4.07 ± 0.57 µM), and 4f (2.98 ± 0.02 µM and 3.80 ± 0.01 µM), respectively, exhibited the strongest activity when compared to the standard reference, butylated hydroxytoluene (BHT) (3.52 ± 0.08 µM and 4.64 ± 0.11 µM). In addition, their anti-inflammatory activity was assessed using the xylene-induced ear edema standard technique and the results demonstrated the potency of 4a, 4b and 4d as excellent anti-inflammatory agents. Preliminary structure–activity relationship studies (SARs) provide those biological activities can be modulated by the presence of unsubstituted aromatic ring as well as the position of substituents on the phenyl moiety via electron withdrawing groups (EWGs) or electron donating groups (EDGs) effects. Docking studies on the most promising compounds 4a, 4b, and 4d into the active sites of S. aureus tyrosyl-tRNA synthetase, Candida albicans N-Myristoyltransferase, Human COX-2 enzyme, and Human Peroxiredoxin 5 revealed good binding profiles with the target proteins. The interaction's stability was further assessed using a conventional atomistic 100 ns dynamic simulation study. Hence, our results recommended the rationalized targets 4a, 4b and 4d, to be promising lead candidates for the discovery of novel dual anti-inflammatory and anti-infection agents.     

Identification of novel oxadiazole-based benzothiazole derivatives as potent inhibitors of α-glucosidase and urease: Synthesis,in vitro bio-evaluation and their in silico molecular docking study

This research work represents a synthetic approach for the development of hybrids derivatives of oxadiazole-based benzothiazole (1–17) and diversity in derivatives was achieved using variety of aryl ring of S-substituted benzothiazole to see the effect on the biological activities. All the synthesized derivatives were evaluated for their in vitro α-glucosidase and urease inhibitory potential. The α-glucosidase and urease inhibition profile of the new derivatives represents moderate to good inhibitory potential with IC₅₀ values ranging from 4.60 ± 1.20 µM to 48.40 ± 7.70 µM (α-glucosidase) and 8.90 ± 2.80 to 57.30 ± 7.70 µM (urease) respectively. The results were compared to standard acarbose (38.60 ± 4.50 µM) and thiourea (58.70 ± 6.80 µM) drugs respectively. Among the synthesized series, the analogs 1 having IC₅₀ values of and 4.60 ± 1.20 (α-glucosidase), 8.90 ± 2.80 (urease) and 2 with IC₅₀ values of 5.60 ± 1.60 (α-glucosidase) and 10.90 ± 2.10(urease) were found to be significantly active against targeted α-glucosidase and urease enzymes. The structure of all the newly synthetics scaffolds were confirmed by using different types of spectroscopic techniques such as HREI-MS, ¹H- and ¹³C- NMR spectroscopy. The molecular docking studies of the synthesized derivatives showed good correlations with the experimental findings. The binding modes of active compounds and their interactions with active site residues revealed them as possible anti-diabetics and anti-urease leads. The degree of activity and docking studies displayed by the novel innovative structural hybrids of oxadiazole-based benzothiazole moieties make these compounds new active leads and promising candidates for the development of anti-diabetics and anti-urease agents.     

Design,synthesis, in vitro and in silico studies of naproxen derivatives as dual lipoxygenase and α-glucosidase inhibitors

A series of 28 novel naproxen derivatives (4a-f, 5a-f, 6a-d, 7a-f, and 8a-f) have been designed, synthesized, and characterized. The synthesized derivatives were assessed as dual inhibitors for 15-lipoxygenase (LOX) and α-glucosidase enzymes and checked for cytotoxicity and ADME studies. The inhibitory potential of naproxen derivatives for 15- LOX was checked through two different methods, the UV absorbance method and the Chemiluminescence method. The biological activities result revealed that through the UV absorbance method, compound 4f (IC₅₀ 21.31 ± 0.32 µM) was found potent among the series followed by compounds 4e (IC₅₀ 36.53 ± 0.51 µM) and 4d (IC₅₀ 49.62 ± 0.12 µM) against standard drug baicalein (IC₅₀ 22.46 ± 1.32 µM) and quercetin (IC₅₀ 2.34 ± 0.35 µM), while through chemiluminescence method tested compounds showed significant 15-LOX inhibition at the range of IC₅₀ 1.13 ± 0.62 µM ?123.47 ± 0.37 µM. Among these compounds, 4e (IC₅₀ 1.13 ± 0.62 µM), 5b (IC₅₀ 1.19 ± 0.43 µM), 8c (IC₅₀ 1.23 ± 0.35 µM) were found most potent inhibitors against quercetin (IC₅₀ 4.86 ± 0.14 µM), and baicalein (IC₅₀ 2.24 ± 0.13 µM). The chemiluminescence method was found more sensitive than the UV method to identify 15-LOX inhibitors. Interestingly all synthesized compounds showed significant α-glucosidase inhibitory activity (IC₅₀ 1.0 ± 1.13 µM ? 367.2 ± 1.23 µM) even better than the standard drug acarbose (IC₅₀ 375.82 ± 1.76 µM), while compound 6c (IC₅₀ 1.0 ± 1.13 µM) and 7c (IC₅₀ 1.1 ± 1.17 µM) were found most potent compounds among the series even many folds better than the standard drug. The cell viability results showed that all compounds were less toxic, maintained cellular viability at the range of 99.8 ± 1.3% to 63.7 ± 1.5%. ADME and molecular docking studies supported drug-likeness and binding interactions of compounds with the targeted enzymes.     

Biology-oriented drug synthesis of nitrofurazone derivatives: Their α-glucosidase inhibitory activity and molecular docking studies

In the present study, twenty (20) structural variants of nitrofurazone were synthesized based on BIODS (Biology-oriented drug synthesis) approach. The structure elucidation of the synthetic molecules (1–20) was carried out using different spectroscopic techniques, and their α-glucosidase inhibitory activity was also determined. The synthetic molecules 1–20 exhibited good α-glucosidase inhibition than the parent, nitrofurazone. Four compounds 2, 4, 6, and 7 showed potential inhibition against α-glucosidase with IC₅₀ values ranging between 0.63 ± 0.25–1.29 ± 0.46 µM as compared to the standard acarbose (IC₅₀ = 2.05 ± 0.41 µM). Nevertheless, compounds 15 (IC₅₀ = 0.74 ± 0.12 µM), and 19 (IC₅₀ = 0.54 ± 0.3 µM) also displayed good α-glucosidase inhibition and compound 19 was the most active compound of the series. Kinetic study of the active compounds 7 and 19 was also carried out to confirm the mode of inhibition. The binding interactions of the most active compounds within the active site of enzyme were determined by molecular docking. Moreover, molecular dynamic simulation of compound 19 was also performed in order to determine the stability of the overall complex (α-glucosidase + c19) in an explicit watery environment. The synthetic molecules were predicted as non-cytotoxic, however, seven compounds 1, 3, 4, 9, 10, 11, and 12 were predicted as carcinogenic.     

Synthesis,in vitro evaluation,and molecular docking studies of benzofuran based hydrazone a new inhibitors of urease

This work has described the synthesis of novel class (1–25) of benzofuran based hydrazone. The hybrid scaffolds (1–25) of benzofuran based hydrazone were evaluated in vitro, for their urease inhibition. All the newly synthesized analogues (1–25) were found to illustrate moderate to good urease inhibitory profile ranging from 0.20 ± 0.01 to 36.20 ± 0.70 µM. Among the series, compounds 22 (IC₅₀ = 0.20 ± 0.01 µM), 5 (IC₅₀ = 0.90 ± 0.01 µM), 23 (IC₅₀ = 1.10 ± 0.01 µM) and 25 (IC₅₀ = 1.60 ± 0.01 µM) were found to be the many folds more potent than thiourea as standard inhibitor (IC₅₀ = 21.86 ± 0.40 µM). The elevated inhibitory profile of these analogues might be due to presence of dihydroxy and flouro groups at different position of phenyl ring B attached to hydrazone skeleton. These dihydroxy and fluoro groups bearing compounds have shown many folds better inhibitory profile through involvement of oxygen of dihydroxy groups in hydrogen bonding with active site of enzymes. Various types of spectroscopic techniques such as ¹H-, ¹³C- NMR and HREI-MS spectroscopy were used to confirm the structure of all the newly developed compounds. To find SAR, molecular docking studies were performed to understand, the binding mode of potent inhibitors with active site of enzymes and results supported the experimental data.     

Molecular docking of phenolic compounds and screening of antioxidant and antidiabetic potential of Olea europaea L. Ethanolic leaves extract

Oxidative stress has a crucial role in diabetic pathophysiology, therefore consuming naturally derived antioxidants as a remedial target. This study examines the naturally occurring antioxidant and antidiabetic of Olea europaea L. ethanolic leaves extract. Olea europaea L. leaves were macerated (OLE) by using absolute ethanol. Phytochemical and physiochemical analysis of OLE was screened using standard methods. The antioxidant effects were examined by DPPH (1, 1-diphenyl-2-picrylhydrazil) radical scavenging assay. In vitro antidiabetic was assayed by α-amylase enzyme inhibition study. Ethanolic extraction of OLE by maceration technique, 10% yield. Loss on drying, foreign organic matters and total ash value of OLE showed 2%, 0.2% and 16.5%, respectively. Phytochemical test on OLE confirmed saponin, flavonoid, glycoside, tannin, phenol and carbohydrate presences. The total phenolic and flavonoid contents of OLE is 490 mg GAE/g and 855 mg RUE/g of extract, respectively. OLE (IC₅₀ 38.37 ± 0.26 µg/ml) showed functional DPPH scavenging assay comparable to ascorbic acid (IC₅₀ 30.37 ± 0.17 µg/ml). In the alpha-amylase inhibitory activity, Acarbose showed an IC₅₀ value of 20.06 ± 0.19 µg/ml, while OLE portrayed an IC₅₀ value of 37.99 ± 0.15 µg/ml. The kinetic studies revealed that all samples at high concentrations reacted within a very short time, and a steady state was reached almost immediately. The lowest concentration showed slow kinetic behaviour implied longer periods before the constant state was reached. Molecular docking studies evidenced that most of the phenolic compounds of OLE interact with the active site of Human pancreatic α-amylase through the hydrogen bonding and hydrophobic interaction confirming the alpha-amylase inhibitory effect. The results suggest that Olea europaea L. has been a conceivable natural bioactive source as an antioxidant and an antidiabetic agent.