Cyclometalated complexes containing ferrocenyl Schiff base: Preparation,characterization, DFT calculations,application in cancer and biological researches and MOE studies

A series of transition metal (II/III) complexes containing organometallic Schiff base ligand (H₂L) had been synthesized and characterized by using elemental analysis (C, H, N, M), molar conductivity, IR, UV–Vis, ¹H NMR and mass spectral analysis. Also, their TG and DTG behaviors were investigated. The ligand was prepared by condensation of 4-aminosalicylic acid with 2-acetylferrocene in 1:1 M ratio. The data of elemental analysis indicated that the prepared complexes were synthesized also in a 1:1 M ratio. The ligand behaved as neutral bidentate ligand that coordinated to metal ions through protonated O-phenolic and protonated carboxylic-OH groups. All complexes had octahedral structure. DFT calculations for H₂L ligand were determined with some parameters such as HOMO-LUMO energy gab, electronegativity and chemical hardness–softness. Antimicrobial activity of both H₂L Schiff base ligand and its metal complexes was tested against different strains of bacteria and fungi species. Furthermore, all compounds had been screened for their anticancer activities against breast cancer (MCF-7) cell line. [Cu(H₂L)(H₂O)₂Cl₂]·2H₂O complex had the lowest IC₅₀ value = 47.3 µg/mL. For determining the more effective and probable binding mode between the H₂L ligand, Co(II) and Zn(II) complexes with different active sites of 4K3V, 2YLB and 3DJD receptors, so molecular docking studies were investigated.     

Synthesis,pharmacological evaluation,and molecular modeling studies of novel isatin hybrids as potential anticancer agents

A novel series of isatin hybrids 5a-g was designed, synthesized, and characterized spectroscopically. The synthesized compounds were evaluated for their cytotoxic activity against the human breast cancer cell line (MCF-7) by in vitro MTT assay. Amongst the tested compounds, 5e compound bearing benzyl moiety at N₄ piperazine was found to be the most active with the promising IC₅₀ (12.47 µM). Moreover, the active compounds 5e and 5g were subjected to antitumor evaluation (in vivo) against Dalton’s ascitic lymphoma (DAL) cell line and the results suggested that the best active compound 5e can normalize the blood picture in comparison to the standard drug. An in silico molecular docking study using the crystal structure of Hsp90 protein described the role of significant protein–ligand interactions and revealed more insights into the binding mode. The drug-likeliness of the compounds was predicted based on Lipinski's rule of five and pharmacokinetic ADME parameters. Hence, the synthesized isatin hybrids could be novel starting point anticancer lead compounds demonstrating drug-like properties which can be explored further for anticancer drug discovery.     

Integrating approach to discover novel bergenin derivatives and phenolics with antioxidant and anti-inflammatory activities from bio-active fraction of Syzygium brachythyrsum

Syzygium brachythyrsum is an important folk medicinal and edible plant in Yunnan ethnic minority community of China, however, little is known about the chemical and bio-active properties. The present study is aimed to identify the bioactive constituents with antioxidant and anti-inflammatory properties by an integrating approach. First, two new bergenin derivatives, brachythol A (1) and brachythol B (2), together with eleven known phenolic compounds (3–13) were isolated from bioactive fractions by phytochemical method. Among these isolated chemicals, five bergenin derivatives, along with 3 phenolics were found in Syzygium genus for the first time. Then, a further chemical investigation based on ultra-high-performance liquid chromatography-Q Exactive Orbitrap mass spectrometry resulted in a total of 107 compounds characterized in the bio-active fractions, including 50 bergenin derivatives, among which 14 bergenin derivatives and 14 phenolics were potential new natural chemicals. Most of the isolated compounds showed obvious antioxidant activities, while compounds 11, 12, and 13 had favorable performance. Eight compounds (2–5, 7, and 9–11) showed good inhibitory activity on nitric oxide (NO) production in macrophage RAW 264.7 cells. The structure–activity correlation analysis indicated that the antioxidation and anti-inflammatory activities enhanced when bergenin was esterified with gallic acid, caffeic acid or ferulic acid. This is the first report of bergenins in Syzygium genus and the richness in new bio-active bergenins and gallic acid derivatives indicated that Syzygium brachythyrsum is a promising functional and medicinal resource.     

Synthesis,spectroscopic study,X-ray diffraction,and comparative antimicrobial study of Schiff bases based on o-toluidine and their Co(II) complexes

Schiff bases are versatile compounds for the design of the ternary complex. An experiment has been made to synthesize two novel complexes of Co(II). Here, The primary ligand, L₁ was prepared by the condensation reaction of o-toluidine with 3-formyl chromone or o-toluidine with 3- methylquinolinecarbaldehyde and the secondary ligand which was 8-Hydroxyquinoline. These potent complexes were prepared by condensation of primary and secondary ligands with Cobalt salt. The reaction was performed through the conventional reflux method. The newly synthesized chromone and quinoline derived novel compounds are proposed to have significant antimicrobial activity against selective strains of bacteria and fungi. This can be great opportunity for researchers and the use of biological applications of the synthesized novel compounds can be a part of unique field of research for the future to be focus. Chromone derivative has great biological diversity in the medicinal and pharmaceutical fields. Along with these compounds, quinoline derivatives also have antibacterial, and antifungal activities. The synthesized ligand and complex were characterized by elemental analysis, molecular weight determination, magnetic moment measurement, melting point determination, spectral analysis (IR, UV–Vis, ¹H NMR, Mass, etc.), and X-ray diffraction. The synthesized complexes were paramagnetic and non-electrolytic in nature. The Uv–Vis, FTIR, NMR, and Mass spectra suggest the octahedral geometry of the complexes. The synthesized compounds were further evaluated for biological studies against selected bacterial and fungal strains. It has been observed that the antimicrobial activity of most of the complexes are better than that of ligands.     

Synthesising injectable molecular self-curing polymer from monomer derived from lignocellulosic oil palm empty fruit bunch biomass: A review on treating Osteoarthritis

Osteoarthritis (OA) is a chronic and irreversible degenerative joint disease that most commonly affects individuals in their forties and fifties worldwide due to the continuously increasing life expectancy. Although joint replacement is an effective remedy for severe end-stage OA, the functional outcomes could be unsatisfactory, while the implants might have a limited lifespan. Due to the drawbacks and limitations of the joint replacement approach, bone Tissue Engineering (TE) is one of the promising bone tissue regeneration technologies that aid in cartilage repair and regeneration and has attracted the attention of experts. The advanced development of biopolymers, in particular biopolymer derived from Oil Palm Empty Fruit Bunch (OPEFB), has been utilised in the fabrication of scaffolds that serve as a crucial component in bone TE. The abundant supply of OPEFB biomass and the increasing trend of converting waste into wealth for environmental sustainability have also provided the opportunity and interest to fully apply biopolymer-derived materials for bone scaffolding and other applications. Therefore, this paper aimed to provide a review of the biopolymers derived from OPEFB for the treatment of OA and other related applications. A brief overview of the biomass sources in Malaysia was presented, followed by a discussion on the chemical compositions and pre-treatment methods of OPEFB by using organosolv pre-treatment and enzymatic hydrolysis for maximum glucose recovery, monomer derived from cellulose OPEFB and synthesizing self-curing polymer scaffold. Additionally, a detailed review of the polymeric biomaterials in bone TE for the fabrication of scaffolds were included in this review. Most importantly, the paper described the potential use of injectable polymeric biomaterials that provide a significant benefit in orthopaedic applications. Overall, this paper provides a perspective on the potential of OPEFB-derived injectable scaffolds as an alternative OA treatment and future bone TE applications.     

The ethnobotanical,phytochemistry and pharmacological activities of Psidium guajava L.

Psidium guajava L., commonly known as guava is an important tropical food plant with diverse medicinal values. In traditional medicine, it is used in the treatment of various diseases such as diarrhoea, diabetes, rheumatism, ulcers, malaria, cough, and bacterial infections. The aim of this review is to provide up-to-date information on the ethnomedicinal uses, bioactive compounds, and pharmacological activities of P. guajava with greater emphasis on its therapeutic potentials. The bioactive constituents extracted from P. guajava include phytochemicals (gallic acid, casuariin, catechin, chlorogenic acid, rutin, vanillic acid, quercetin, syringic acid, kaempferol, apigenin, cinnamic acid, luteolin, quercetin-3-O-α-L-arabinopyranoside, morin, ellagic acid, guaijaverin, pedunculoside, asiastic acid, ursolic acid, oleanolic acid, methyl gallate and epicatechin) and essential oils (limonene, trans-caryophyllene, α-humulene, γ-muurolene, selinene, caryophyllene oxide, bisabolol, isocaryophyllene, δ-cadinene, α-copaene, α-cedrene, β-eudesmol, α-pinene, β-pinene, β-myrcene, linalool, α-terpineol and eucalyptol). In vitro and in vivo studies demonstrated that P. guajava possesses pharmacological activities such as antidiabetic, antidiarrhoeal, hepatoprotective, anticancer, antioxidant, anti-inflammatory, antiestrogenic, and antibacterial activities which support its traditional uses. The exhibited pharmacological activities reported may be attributed to the numerous bioactive compounds present in different parts of P. guajava. Based on the beneficial effects of P. guajava as well as its bioactive constituents, it can be exploited in the development of pharmaceutical products and functional foods. However, there is a need for comprehensive studies in clinical trials to establish the safe doses and efficacy of P. guajava for the treatment of several diseases.     

Synthesis,bioactivity and preliminary mechanism of action of novel trifluoromethyl pyrimidine derivatives

In this study, a series of trifluoromethyl pyrimidine derivatives 5a-5v were designed and synthesized. All synthetic compounds were original. Bioassay results showed that some of the target compounds were proved to have higher antiviral and antifungal activities than those of commercial agents. Especially, EC₅₀ values of the curative activity of compound 5j and the protection activity of compound 5m were 126.4 and 103.4 µg/mL, respectively, which were lower than that of ningnanmycin. Microscale thermophoresis experiment proved that there was a good interaction between compound 5m and TMV-CP. Meanwhile, the antifungal activity results showed that compound 5u had a significant on in vitro against Rhizoctonia solani (RS) activity, with the EC₅₀ value of 26.0 µg/mL, which was equal to that of azoxystrobin. As well, in vivo experiments on rice leaves showed that compound 5u could effectively control RS, and the effect of 5u on the cell morphology of RS was observed by scanning electron microscopy.     

Chemical profiling of Verbena officinalis and assessment of its anti-cryptosporidial activity in experimentally infected immunocompromised mice

Cryptosporidiosis is a global zoonotic infection that causes water-borne epidemics of diarrhea. Nevertheless, there are few available therapies for cryptosporidiosis. However, the gold standard drug nitazoxanide (NTZ) has limited efficacy in malnourished and immunocompromised patients. Furthermore, Verbena officinalisL. is a herbal plant widely used in traditional medicine to cure several health disorders and is recognized to possess numerous therapeutic applications. In the present study, the phytochemical composition of aerial part extract from Verbena officinalis was investigated via LC-ESI-MS/MS.Furthermore, the anti-cryptosporidial activity was also performed using an animal model. Fifty mice were divided into 5 groups; GI: non-infected (Negative control), GII: infected non treated (positive control), GIII: infected, treated with NTZ, GIV: infected, treated with V. officinalis n-butanol extract, GV: infected, treated with a combination of NTZ and V. officinalis. Parasitological examination revealed a highly significant difference (P-value < 0.001) between GIII, GIV, and GV compared to GII regarding the mean number of Cryptosporidium spp. oocyst in the stool. Moreover, GV showed the best efficacy with a percentage of 87%. Also, histopathological examination showed variable degrees of improvement in the villous broadening, and the inflammatory infiltrates in the small intestine with a reduction of hepatocyte degeneration and mononuclear infiltration in GIII, GIV, and GV compared to GII, with the best results seen in GV. Additionally, the chemical profiling of n-butanol extract identified 16 secondary metabolites comprising flavonoids, phenolic acids, phenylethanoids, and coumarins. In conclusion, V. officinalis is an intrinsic supplier of biologically active metabolites with outstanding anti-parasitic and possible anti-inflammatory effects.     

Synthesis,antifungal activity and in vitro mechanism of novel 1-substituted-5-trifluoromethyl-1H-pyrazole-4-carboxamide derivatives

Inspired by the wide application of amides in plant pathogens, a series of novel 1-substituted-5-trifluoromethyl?1H?pyrazole-4-carboxamide derivatives were designed and synthesized. Bioassay results indicated that some target compounds exhibited excellent and broad-spectrum in vitro and certain in vivo antifungal activities. Among them, the in vitro EC₅₀ values of Y₁₃ against G. zeae, B. dothidea, F. prolifeatum and F. oxysporum were 13.1, 14.4, 13.3 and 21.4 mg/L, respectively. The in vivo protective activity of Y₁₃ against G. zeae at 100 mg/L was 50.65%. SAR analysis revealed that the phenyl on the 1-position of the pyrazole ring was important for this activity. An antifungal mechanism study of Y₁₃ against G. zeae demonstrated that this compound may disrupt the cell membrane of mycelium, thus inhibiting the growth of fungi. These mechanistic study results were inconsistent with those for traditional amides and may provide a novel view for deep study of this series of pyrazole carboxamide derivatives.     

Chemical composition,antioxidant, antimicrobial and antiproliferative activity of Laureliopsis philippiana essential oil of Chile,study in vitro and in silico

Chilean Laureliopsis philippiana has been used in traditional medicine by the Mapuche and their ancestors. To evaluate its pharmacological activity, Laureliopsis philippiana leaf essential oil extract (LP_EO) was chemically and biologically characterized in the present study. In vitro antioxidant potential was analyzed, and antitumor activity was evaluated in non-tumor and tumor cell culture lines. Caenorhabditis elegans was used as a model for evaluating toxicity, and the chemical composition of the essential oil was analyzed using gas chromatography–mass spectrometry. The oil contains six major monoterpenes: eucalyptol (27.7 %), linalool (27.6 %), isozaphrol (19.5 %), isohomogenol (12.6 %), α-terpineol (7.7 %), and eudesmol (4.8 %). Based on quantum mechanical calculations, isosafrole and isohomogenol conferred in vitro antioxidant and antimicrobial activity to LP_EO. In addition, LP_EO showed antimicrobial activity against clinical Helicobacter pylori isolates (MIC 64 and MBC > 128 μg·mL^?1), Staphylococcus aureus (MIC 32 and MBC > 64 μg·mL^?1), Escherichia coli (MIC 8 and MBC 16 μg·mL^?1) and Candida albicans (MIC 64 and > 128 μg·mL^?1). LP_EO could selectively inhibit the proliferation of epithelial tumor cell lines but showed low toxicity against Caenorhabditis elegans (0.39 to 1.56 μg·mL^?1). Therefore, LP_EO may be used as a source of bioactive compounds in novel pharmacological treatments for veterinary and human application, cosmetics, or sanitation.     

QSAR based virtual screening derived identification of a novel hit as a SARS CoV-229E 3CLpro Inhibitor: GA-MLR QSAR modeling supported by molecular Docking,molecular dynamics simulation and MMGBSA calculation approaches

Congruous coronavirus drug targets and analogous lead molecules must be identified as quickly as possible to produce antiviral therapeutics against human coronavirus (HCoV SARS 3CLpro) infections. In the present communication, we bear recognized a HIT candidate for HCoV SARS 3CLpro inhibition. Four Parametric GA-MLR primarily based QSAR model (R2:0.84, R2adj:0.82, Q2loo: 0.78) was once promoted using a dataset over 37 structurally diverse molecules along QSAR based virtual screening (QSAR-VS), molecular docking (MD) then molecular dynamic simulation (MDS) analysis and MMGBSA calculations. The QSAR-based virtual screening was utilized to find novel lead molecules from an in-house database of 100 molecules. The QSAR-vS successfully offered a hit molecule with an improved _PEC₅₀ value from 5.88 to 6.08. The benzene ring, phenyl ring, amide oxygen and nitrogen, and other important pharmacophoric sites are revealed via MD and MDS studies. Ile164, Pro188, Leu190, Thr25, His41, Asn46, Thr47, Ser49, Asn189, Gln191, Thr47, and Asn141 are among the key amino acid residues in the S1 and S2 pocket. A stable complex of a lead molecule with the HCoV SARS 3CLpro was discovered using MDS. MM-GBSA calculations resulted from MD simulation results well supported with the binding energies calculated from the docking results. The results of this study can be exploited to develop a novel antiviral target, such as an HCoV SARS 3CLpro Inhibitor.     

Dynamic variations of bioactive compounds driven by enzymes in Psoralea corylifolia L. from growth to storage and processing

Fructus Psoraleae (FP), the dried ripe fruit of Psoralea corylifolia L., is a popular herbal medicine commonly applied for alleviating osteoporosis and vitiligo. But, until now, the dynamic variations of compounds in P. corylifolia have been less investigated during its growth, storage, and treatment by different temperatures, which is meaningful for guaranteeing the quality of FP. In this study, focused on these questions, with emphasis on the enzyme-driven dynamic transformation of coumarins, ultra-high performance liquid chromatography coupled with photodiode array detector (UHPLC-PDA) method was successfully established for the simultaneous determination of nine compounds. The distribution and accumulation of compounds were discussed and illuminated in different parts of P. corylifolia and samples harvested at different times. The characteristics of compounds' variation in flowers and fruits of P. corylifolia were identified. Through the market survey and quantitative study on FP, positive correlation was speculated between transformation from (iso)psoralenoside to (iso)psoralen via β-glucosidase and storage time, which was further confirmed by accelerated stability test. The effect of treated temperatures (40–210 °C) was unveiled on the enzyme activity and transformation from (iso)psoralenoside to (iso)psoralen in FP. And the focused compounds' transformation was mainly driven by β-glucosidase when the temperature was below 120 °C. Above 120 °C, β-glucosidase was completely inactivated, and the focused compounds' transformation was mediated by high-temperature, also the obvious degradation was found. Our results demonstrated that compounds' transformation characteristics arising from the growth, processing and storage of P. corylifolia are critical factors to ensure the quality of FP.     

Tuning of graphitic carbon nitride (g-C3N4) for photocatalysis: A critical review

Graphitic carbon nitride (g-C₃N₄) is a remarkable semiconductor catalyst that has attracted widespread attention as a visible light photo-responsive, metal-free, low-cost photocatalytic material. Pristine g-C₃N₄ suffers fast recombination of photogenerated electron-hole pairs, low surface area, and insufficient visible light absorption, resulting in low photocatalytic efficiency. This review presents the recent progress, perspectives, and persistent challenges in the development of g-C₃N₄-based photocatalytic materials. Several approaches employed to improve the visible light absorption of the materials including metal and non-metal doping, co-doping, and heterojunction engineering have been extensively discussed. These approaches, in general, were found to decrease the material’s bandgap, increase the surface area, reduce charge carrier recombination, and promote visible light absorption, thereby enhancing the overall photocatalytic performance. The material has been widely used for different applications such as photocatalytic hydrogen production, water splitting, CO₂ conversion, and water purification. The work has also identified various limitations and weaknesses associated with the material that hinders its maximum utilization under visible illumination and presented state-of-the-art solutions that have been reported recently. The summary presented in this review would add an invaluable contribution to photocatalysis research and facilitate the development of efficient visible light-responsive semiconducting materials.     

Production of bioactive compounds from callus of Pueraria thomsonii Benth with promising cytotoxic and antibacterial activities

For thousands of years Pueraria thomsonii Benth has been used to treat a number of diseases in traditional Chinese pharmacopeia. Despite these uses, there is still insufficient information on its biological activity and chemical composition. In this respect, the in vitro callus culture of P. thomsonii was subjected to identify anticancer and antibacterial compounds. Based on significant preliminary cytotoxicity and antibacterial activities; the chemical investigation led to the isolation of isoflavonoids, coumaric acid derivative and dihydroxyflavanone-type of compounds viz., daidzin (1), puerarin (2), biochanin A (3), daidzein (4), p-coumaric acid ethyl ester (5) and liquiritigenin (6), respectively. These compounds were tested for their cytotoxicity and antibacterial activities. Among them, p-coumaric acid ethyl ester (5) exhibited significant cytotoxicity with GI₅₀ values of 14.73, 15.64 and 20.88 μM/mL against 4T1, NC1-H1975 and A549, respectively; the other isoflavones and aflavonoid showed moderate to weak activities. Moreover, p-coumaric acid ethyl ester (5) inhibited the growth of K. pneumonia, MRSE and MRSA at very low MIC values of 6.01, 12.01 µg/mL 24.02, respectively. On the other hand compounds biochanin A (3) and liquiritigenin (6) showed moderate antibacterial activity. Because of the potential anticancer and antibacterial activities of bioactive compounds from P. thomsonii, they can be used to treat various cancer and emerging bacterial infections.     

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).     

Basic characterization and Alzheimer’s disease relieving property of a glucose riched polysaccharide from Cibotium barometz

The water-soluble polysaccharides from plants have attracted ever-increasing attention in the field of food and drug due to their various activities and low toxicity. CBP50-1, as a purified fraction of polysaccharide from the rhizome of Cibotium barometz (CBP), mainly consisted of glucose (55.45%) and xylose (25.27%). CBP50-1 showed excellent antioxidant activity for scavenging 2,2?Diphenyl?1?picryl?hydrazy (DPPH) radical and hydroxyl radical, further inhibiting lipid peroxidation. CBP50-1 significantly improved the survival rate of Caenorhabditis elegans under thermal and oxidative stress. Furthermore, CBP50-1 reduced the paralysis and oxidative damage induced by amyloid-beta (Aβ) and increased the antioxidant enzyme activity in Alzheimer’s disease (AD) model C. elegans CL4176 through c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) signal pathway. Thus, CBP50-1 had a potential application in health industries.     

Preparation and characterization of a novel magnetized nanosphere as a carrier system for drug delivery using Plantago ovata Forssk. hydrogel combined with mefenamic acid as the drug model

The aim of the present study was to magnetize Plantago ovata Forssk. hydrogel and produce a nanosphere system to carrier mefenamic acid as the drug model. For this propose, P. ovata seeds hydrogel (POSH) was extracted and magnetized by Fe₃O₄ being functionalized using tetraethyl orthosilicate and trimethoxyvinysilane. Thereafter, mefenamic acid (MFA) was loaded on the carrier system. The final product, as the magnetic drug loaded nanosphere (Fe/POSH/MFA), was fully characterized through different techniques involving X-ray diffraction (XRD), scanning electron microscopy (SEM), vibrating-sample magnetometer (VSM), thermal gravimetric analysis (TGA), dynamic light scattering (DLS), and FT-IR spectroscopy. The results confirmed the successful production of the drug loaded nanosphere system with particles magnetization of 25 emu/g over a range size of 40–50 nm. However, the size distribution less than 100 nm was measured through DLS analysis. The hydrogel showed a pH sensitivity swelling behavior representing the best efficacy at pH 7.4. The efficiency of the drug encapsulation was found to be 64.35%. The drug releasing was studied using a dialysis bag at pH = 7.4. The highest in vitro drug releasing was found to be 57.3 ± 0.6% after 72 h, as well. The findings of the current report account for the potential use of P. ovata hydrogel as an effective delivery system for encapsulation of water insoluble basic drugs, e.g., MFA in a magnetized carrier system.     

Pharmacophore model-aided virtual screening combined with comparative molecular docking and molecular dynamics for identification of marine natural products as SARS-CoV-2 papain-like protease inhibitors

Targeting SARS-CoV-2 papain-like protease using inhibitors is a suitable approach for inhibition of virus replication and dysregulation of host anti-viral immunity. Engaging all five binding sites far from the catalytic site of PLpro is essential for developing a potent inhibitor. We developed and validated a structure-based pharmacophore model with 9 features of a potent PLpro inhibitor. The pharmacophore model-aided virtual screening of the comprehensive marine natural product database predicted 66 initial hits. This hit library was downsized by filtration through a molecular weight filter of ≤ 500 g/mol. The 50 resultant hits were screened by comparative molecular docking using AutoDock and AutoDock Vina. Comparative molecular docking enables benchmarking docking and relieves the disparities in the search and scoring functions of docking engines. Both docking engines retrieved 3 same compounds at different positions in the top 1 % rank, hence consensus scoring was applied, through which CMNPD28766, aspergillipeptide F emerged as the best PLpro inhibitor. Aspergillipeptide F topped the 50-hit library with a pharmacophore-fit score of 75.916. Favorable binding interactions were predicted between aspergillipeptide F and PLpro similar to the native ligand XR8-24. Aspergillipeptide F was able to engage all the 5 binding sites including the newly discovered BL2 groove, site V. Molecular dynamics for quantification of Cα-atom movements of PLpro after ligand binding indicated that it exhibits highly correlated domain movements contributing to the low free energy of binding and a stable conformation. Thus, aspergillipeptide F is a promising candidate for pharmaceutical and clinical development as a potent SARS-CoV-2 PLpro inhibitor.     

Camellia sinensis: Insights on its molecular mechanisms of action towards nutraceutical,anticancer potential and other therapeutic applications

The Camellia sinensis plant provides a wide diversity of black, green, oolong, yellow, brick dark, and white tea. Tea is one of the majorly used beverages across the globe, succeeds only in the water for fitness and pleasure. Generally, green tea has been preferred more as compared to other teas due to its main constituent e.g. polyphenols which contribute to various health benefits. The aim of this updated and comprehensive review is to bring together the latest data on the phytochemistry and pharmacological properties of Camellia sinensis and to highlight the therapeutic prospects of the bioactive compounds in this plant so that the full medicinal potential of Camellia sinensis can be realised. A review of published studies on this topic was performed by searching PubMed/MedLine, Scopus, Google scholar, and Web of Science databases from 1999 to 2022. The results of the analysed studies showed that the main polyphenols of tea are the four prime flavonoids catechins: epigallocatechin gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC), and epicatechin (EC) along with the beneficial biological properties of tea for a broad heterogeneity of disorders, including anticancer, neuroprotective, antibacterial, antiviral, antifungal, antiobesity, antidiabetes and antiglaucoma activities. Poor absorption and low bioavailability of bioactive compounds from Camellia sinensis are limiting aspects of their therapeutic use. More human clinical studies and approaching the latest nanoformulation techniques in nanoparticles to transport the target phytochemical compounds to increase therapeutic efficacy are needed in the future.     

Pentacyclic Triterpenoids,Phytosteroids and Fatty Acid Isolated from the Stem-bark of Cola lateritia K. Schum. (Sterculiaceae) of Cameroon origin; Evaluation of Their Antibacterial Activity

The phytochemical investigation on the chemical constituents of dichloromethane-methanol (1:1) stem-bark extract of Cola lateritia K. Schum. (Sterculiaceae) led to the isolation and characterization of five pentacyclic triterpenoids, one fatty acid and two phytosteroids. The compounds were identified as heptadecanoic acid (1), maslinic acid (2), betulinic acid (3), lupenone (4), lupeol (5), friedelin (6), β-stigmasterol (7) and ß-sitosterol-3-O-ß-D-glucoside (8). Their structures were determined by NMR analysis (¹H, ¹³C, DEPT-135, COSY, HMBC and HSQC), high-resolution mass spectrometry (HR-ESI-MS) and comparisons with published data in the literature. This work, to the best of our knowledge, is the first isolation and identification of these compounds in pure forms from Cola lateritia. Also, compounds 1–3 are reported for the first time from Cola genus. In vitro antibacterial activity of the isolated compounds (1–8) and the crude extract were evaluated against Bacillus subtilis, Staphylococcus epidermidis, Enterococcus faecalis, Mycobacterium smegmatis, Staphylococcus aureus, Enterobacter cloacae, Klebsiella oxytoca, Proteus vulgaris, Klebsiella pneumonia, Escherichia coli, Proteus mirabilis and Klebsiella aerogenes with streptomycin, nalidixic acid and ampicillin as standard antibacterial drugs. Compound 2 was active against E. faecalis (MIC = 18.5 µg/mL), and it was 6.9 and 28 times lower and active than that of streptomycin (MIC 128 µg/mL) and nalidixic acid (MIC > 512 µg/mL) respectively. All the isolated compounds and crude extract showed significant activities against the tested bacterial strains.