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).     

Saccharonol B,a new cytotoxic methylated isocoumarin from Saccharomonospora azurea

From an antimicrobial gram-positive actinomycete strain of Saccharomonospora azurea (MTCC11714) isolated from high altitude soil of Kargil (J&K, India), a new isocoumarin saccharonol B (2) along with two known compounds viz. saccharonol A (1) and piericidin A₃ (3) was isolated and characterized. The structure of the new compound was established based on extensive 2D-NMR data. Saccharonol B (2) exhibited mild antimicrobial activity against a standard panel of microorganisms Staphylococcus aureus ATCC 29213, Candida albicans ATCC 90028, and Aspergillus fumigatus MTCC 1811 with MIC values in the range of 128–248 μg/mL. Saccharonol B (2) and piericidin A₃ (3) showed selective cytotoxic activity against human pancreatic carcinoma cell line (MIAPaCa-2) with IC₅₀ values of 9 and 8 μM, respectively. Mechanistic studies indicated that saccharonol B (2) arrests S-phase of the cell cycle and causes dose-dependent loss of mitochondrial potential in MIAPaCa-2 cells.     

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.     

Synthesis and fungicidal activity of novel 1,2,4-triazole derivatives containing a pyrimidine moiety

Abstract

A series of novel 1,2,4-triazole derivatives containing a pyrimidine moiety were synthesized and their fungicidal activities were evaluated. The preliminary biological test indicated that some of the target compounds exhibited moderate to good fungicidal activities against the tested plant pathogenic fungi compared with the commercial agent. Among them, compounds 9n and 9o exhibited excellent antifungal activity against Phompsis sp., with the half-maximal effective concentration (EC₅₀) values of 25.4 and 31.6?μg/mL, which were even better than the commercial agent of Pyrimethanil (32.1?μg/mL). Meanwhile, compound 9o showed better fungicidal activities against B. dothidea and B. cinerea with 40.1 and 55.1?μg/mL, respectively, in comparison with that of commercial Pyrimethanil (57.6 and 62.8?μg/mL).     

Potent antibacterial agents: pyridinium-functionalized amphiphiles bearing 1,3,4-oxadiazole scaffolds

Through tuning and optimizing the phenyl substituents and alkyl length, a series of pyridinium-functionalized amphiphiles possessing potent antibacterial activity toward three types of plant pathogenic bacteria were obtained. Investigations on the inhibition effect of substituents on the phenyl ring towards the bioactivity suggested that the substitutional group was not the crucial factor for the bioactivity. In comparison, the antibacterial effects could be significantly enhanced with increasing the length of alkyl chains. Among these amphiphiles, 6c, 6f, 6h, 6i, 6k, 6l, 6n, and 6q exhibited remarkable inhibition activities against the three pathogenic bacteria with the half-maximal effective concentration (EC₅₀) values within 0.128–1.98 µg/mL. Furthermore, the minimum EC₅₀ values against the pathogens Xanthomonas oryzae pv. oryzae and Xanthomonas axonopodis pv. citri could reach to 0.128 and 0.403 µg/mL, respectively, which were decreased about four times than those of our previous results. Given their simple synthesis and biocidal antibacterial activity, this kind of amphiphiles could be developed as promising bactericides against plant bacterial diseases.     

Green synthesis of novel quinoline based imidazole derivatives and evaluation of their antimicrobial activity

We have described the conventional and microwave method for the synthesis of N-(4-((2-chloroquinolin-3-yl)methylene)-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl)(aryl)amides 3a–l. It is observed that the solvent-free microwave thermolysis is a convenient, rapid, high-yielding, and environmental friendly protocol for the synthesis of quinoline based imidazole derivatives when compared with conventional reaction in a solution phase. Antimicrobial activity of the newly synthesized compounds is screened in vitro on the following microbial cultures: Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 1688), Staphylococcus aureus (MTCC 96), Streptococcus pyogenes (MTCC 442), Candida albicans (MTCC 227), Aspergillus niger (MTCC 282), Aspergillus clavatus (MTCC 1323). All the synthesized bio-active molecules are tested for their in vitro antimicrobial activity by bioassay namely serial broth dilution. Among these compounds 3c, 3d, 3f, 3h and 3j show significant potency against different microbial strains. All the compounds have been characterized by IR, ¹H NMR, ¹³C NMR and mass spectral data. On the basis of statistical analysis, it is observed that these compounds give significant co-relation.     

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.     

Synthesis,antiviral activity,and 3D-QSAR study of novel chalcone derivatives containing malonate and pyridine moieties

Several novel chalcone derivatives containing malonate and pyridine moieties were synthesized, and their structures were confirmed by ¹H nuclear magnetic resonance, ¹³C nuclear magnetic resonance, ¹⁹F nuclear magnetic resonance, infrared, and elemental analyses. Antiviral bioassays revealed that most of the compounds exhibited good antiviral activity against cucumber mosaic virus (CMV) at 500 μg/mL. In particular, compounds 5l and 5n showed significant curative activities against CMV in vivo with 50% effective concentration (EC₅₀) values of 186.2 and 211.5 μg/mL, respectively; these values are even better than that of ningnanmycin (330.5 μg/mL). A 3D quantitative structure–activity relationship study was carried out using the comparative molecular field analysis technique based on curative activities against CMV. Results revealed good predictive ability with cross-validated q² and non-cross-validated r² values of 0.517 and 0.990, respectively.     

Design,synthesis, antimicrobial evaluations and in silico studies of novel pyrazol-5(4H)-one and 1H-pyrazol-5-ol derivatives

A new series of 1,4-disubstituted 3-methylpyrazol-5(4H)-one derivatives were synthesized by reacting various substituted aromatic aldehydes with 3-methylpyrazol-5(4H)-one derivatives through Knoevenagel condensation by conventional as well as by exposure to microwave irradiations. After that newly synthesized compounds of 1,4-disubstituted 3-methyl-1H-pyrazol-5-ol were prepared from these derivatives by reduction reaction of sodium borohydride at 0–5 °C. Sixty-four heterocyclic compounds containing a pyrazole moiety were synthesized with good to excellent yields (51 to 91%). Compounds (3d, 3m, 4a, 4b, 4d, and 4g) showed potent antibacterial activity against MSSA (Methicillin-susceptible strains of Staphylococcus aureus) and MRSA (Methicillin-resistant strains of Staphylococcus aureus) with MIC (the minimum inhibitory concentration) ranging between 4 and 16 µg/mL as compared to ciprofloxacin (MIC = 8–16 µg/mL). Compounds (4a, 4h, 4i, and 4l) showed potent antifungal activity against Aspergillus niger with MIC ranging between 16 and 32 µg/mL as compared to fluconazole (MIC = 128 µg/mL). In particular, compound 4a exhibited the strongest activity among the synthesized compounds in both bacterial and fungal strains with MIC ranging between 4 and 16 µg/mL. Furthermore, the nine most active compounds showed a good ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile in comparison to ciprofloxacin and fluconazole as reference drugs. Molecular docking predicted that DHFR (dihydrofolate reductase) protein from Staphylococcus aureus and NMT (N-myristoyl transferase) protein from Candida albicans are the most suitable targets for the antimicrobial activities of these potent compounds.     

[Cd(Sn9)2]6− and [Cd(Ni@Sn9)2]6−: Reactivity and coordination chemistry of empty and Ni-centered [Sn9]4− Zintl ions

To investigate the reactivity of homoatomic clusters [E₉]^4? (E = Si-Pb) and intermetalloid clusters [M@E₉]^q?, the reactions of the Zintl anions [Sn₉]^4? and [Ni@Sn₉]^4? with the CdMes₂ (Mes = Mesitylene) in the presence of 2.2.2-crypt were carried out. Two new compounds [K(2.2.2-crypt)]₆[(Sn₉)Cd(Sn₉)]·en (1) and [K(2.2.2-crypt)]₆[(Ni@Sn₉)Cd(Ni@Sn₉)]·en (2) were afforded. Both 1 and 2 were characterized by single-crystal X-ray diffraction, energy dispersive X-ray (EDX), and electrospray ionization mass spectrometry (ESI-MS), and can be viewed as two [Sn₉]^4? or [Ni@Sn₉]^4? subunits bridged by Cd ion in an η³:η³ coordination mode. Quantum chemical calculations reveal the relationships between the geometries and electronic structures of clusters 2a, [Ni₃Ge₁₈]^4? and [Cu₄@Sn₁₈]^4?. Further electron localization technique (AdNDP method) was performed to explain chemical bonding patterns of 1a.     

Assessment of antimicrobial and enzymes inhibition effects of Allium kastambulense with in silico studies: Analysis of its phenolic compounds and flavonoid contents

Type 2 diabetes and obesity-related metabolic diseases have been treated with traditional medicinal plants for centuries. In this study, the effects of Allium kastambulense plant extracts on different enzyme activities were investigated, and the results were added as graphics and tables after calculating. This study aimed to identify and quantify the phenolic composition of Allium kastambulense Bosse and determine the anti-lipase, anti-urease, anti-melanogenesis, antidiabetic, anti-alzheimer, and antibacterial properties. IC₅₀ results for all enzymes were obtained between 0.55 and 138 µg/mL, and this plant inhibited HMG_CoA R and tyrosinase enzymes more with IC₅₀ values of 0.55 and 59.17 µg/mL, respectively. The interactions of active compounds showing activity against different enzymes were examined with molecular docking studies. The most active compound 3, (rosmarinic acid) has ?10.90 kcal/mol binding energy value against HMG_CoA R, and also the potential structure compound 2, (+catechin), which has activity against α-amylase, α-glycosidase, and lipase enzymes, was –8.30, ?8.40 and ?9.70 kcal/mol, respectively. Finally, antimicrobial effects, total phenolic, and flavonoid content, determined with its higher total phenolic (22.63 mg GAE/g extract) and flavonoid (6.41 mgQE/g extract) contents and main chemical compounds of this plant were gentisic acid, (+) catechin, and rosmarinic acid, respectively.     

Antitubercular and antioxidant activities of hydroxy and chloro substituted chalcone analogues: Synthesis,biological and computational studies

A series of chalcone analogues (1–15) were synthesized by Claisen-Schmidt condensation in good yields (70–95%) and characterized by FT-IR, ¹H NMR and mass spectral methods. Additionally, compounds 3 and 7 were characterized by ¹³C NMR. Antitubercular and antioxidant activities of the chalcones were evaluated by MABA and DPPH free radical assays. In MABA assay analogues 3 (MIC = 14 ± 0.11 µM) and 11 (MIC = 14 ± 0.17 µM) bearing fluorine and methoxy groups at para and meta positions were 1.8-times more active than the standard pyrazinamide (MIC = 25.34 ± 0.22 µM). The chalcone analogues such as compound 7 (IC₅₀ = 4 ± 1 µg/mL) containing electron releasing groups such as OH at ortho position had slightly more antioxidant activity than Gallic acid (IC₅₀ = 5 ± 1 µg/mL). The potential compounds 3, 7, 9 and 11 were less selective and toxic against human live cell lines-LO2. Further, molecular docking results of chalcones against anti-tubercular drug target isocitrate lyase (PDB ID: 1F8M) revealed that compound 3 and 11 shown least binding energies as ?7.6, and ?7.5 kcal/mol are in line with in vitro MABA assay, suggesting that these compounds 3 and 11 are strong inhibitor of isocitrate lyase. SwissADME programme estimated the drug likeliness properties of compounds 3, 7, 9 and 11. The lead molecules arisen through this study helps to develop new antitubercular and antioxidant agents.     

Synthesis and antiviral bioactivity of novel chalcone derivatives containing purine moiety

A series of novel chalcone derivatives containing purine group was synthesized and evaluated for their antiviral activities against cucumber mosaic virus and tobacco mosaic virus. Compound 3o exhibited remarkable antiviral activities and strong combining capacity to tobacco mosaic virus coat protein.     

Synthesis and comparative study of cytotoxicity and anticancer activity of Chalconoid-Co(II) metal complexes with 2-hydroxychalcones analogue containing naphthalene moiety

A series of six C1–C6 chalconoid based Co(II) complexes were prepared from bi-dentate 2-hydroxychalcones ligands L1-L6 containing naphthalene moiety. All synthesized metal-complexes have been evaluated to determine their cytotoxicity and anticancer activity against liver cancer cell line (Hep G2). Compared to standard 5-fluorouracil (IC₅₀ ?= ?98.61 ?μg/mL), the metal complex C6 exhibits more potency with IC₅₀ value 64.21 ?μg/mL against liver cancer cell line. While the remaining metal complexes such as C2, C4 and C5 are moderately active with IC₅₀ value 314.93, 414.05 and 376.00 ?μg/mL respectively. The complexes C1 and C3 with IC₅₀ value ?> ?1000 ?μg/mL are inadequate to display anticancer activity against Hep G2. Our perception towards the presence of organic group in the main structural moiety of complex C6 which associated with di-hydroxy (-OH) substituent at 3 and 4-position found more potent than complex C2, C4 and C5 which associated with halo (-Cl) substituent. The MTT assay revealed that the cytotoxicity and anticancer activity enhanced upon coordination of bio-ligand compared to free chalcone ligands. Therefore the present study may lead to the development of new class of anticancer drugs with structural modification.     

Synthesis and evaluation of N-(4-(substituted)-3-(trifluoromethyl) phenyl) isobutyramides and their N-ethyl analogous as anticancer,anti-angiogenic & antioxidant agents: In vitro and in silico analysis

N-(4-(substituted)-3-(trifluoromethyl) phenyl) isobutyramides and their N-ethyl analogues (flutamides) are versatile scaffolds with a wide spectrum of biological activities. A series of new N-(4-(substituted)-3-(trifluoromethyl) phenyl) isobutyramides (8a-t) and their N-ethyl analogous (9a-t) were synthesized and characterized. The inhibitory potential of the synthesized compounds on the viability of three human cancer cell lines HEP3BPN 11 (liver), MDA-MB 453 (breast), and HL 60 (leukemia) were assessed. Among all the compounds 8 L, 8q, 9n and 9p showed higher inhibitory activity on the viability of HL 60 than the standard methotrexate. These lead molecules were then tested for their potential to inhibit the activity of proangiogenic cytokines. The compound 9n showed significantly better inhibition against two cytokines viz. TNFα and Leptin as compared to the standard suramin, while 9p has activity comparable to suramin against IGF1, VEGF, FGFb, and Leptin. The 8q is found to be strong antiangiogenic agent against IGF1, VEGF and TGFβ; while 8 L has showed activity against TNFα, VEGF, and Leptin inhibition. Furthermore antioxidant potential of 8a–t and 9a-t compounds was screened using DPPH, OH and SOR radical scavenging activities. The OH radical scavenging activity of 8c and DPPH activities of 9n as well as 9o are significant as compared to respective standards ascorbic acid and α-tocopherol. The 8c, 9p and 9 h have also exhibited potential antioxidant activity. Additionally, we present in silico molecular docking data to provide the structural rationale of observed TNFα inhibition against newly synthesized compounds. Overall, the synthesized flutamide derivatives have not only anticancer activity, but also possess dual inhibitory effect (anti-angiogenesis and antioxidant) and hence can act as a promising avenue to develop further anticancer agents.     

Green and Efficient Synthesis of 4‐Heteryl‐Quinolines and Their Antibacterial Evaluations

A green and efficient synthesis of 4‐heteryl‐quinolines ( 9a , 9b , 9c , 9d ), ( 10a , 10b , 10c , 10d ) and ( 11a , 11b , 11c , 11d ) has been described using PEG‐600 as a green solvent. Initially, 4‐chloro‐2‐methylquinolines ( 5a , 5b , 5c , 5d ) on reaction with aromatic heterocyclic thiols ( 6 ), ( 7 ), and ( 8 ) using PEG‐600 at 100°C for 30–40 min resulted in ( 9 ), ( 10 ), and ( 11 ) in good yields. Alternatively, ( 9 ), ( 10 ), and ( 11 ) could also be prepared in dimethylformamide using K2CO3 as base and tetrabutylammonium bromide as phase transfer catalyst at 100°C for 1–2 h. All the compounds were synthesized and characterized by IR, NMR, mass spectroscopy, and 13C NMR analysis. All synthesized compounds were screened for their antibacterial activity against clinical strains that include Gram‐positive (Bacillus subtilis MTCC 121, staphylococcus aureus MLS‐16 MTCC 2940, Micrococcus lutes MTCC 2470, and Staphylococcus aureus MTCC 96) and Gram‐negative bacteria (Candida albicans MTCC 3017, Klebsiella planticola MTCC 530, Escherichia coli MTCC 739, and Pseudomonas aeruginosa MTCC 2453). The results revealed that compounds ( 9a , 9d , 10a , 10c , 11b , and 11d ) exhibited significant antibacterial activity almost equal to the standard drug, that is, Ciprofloxacin.     

Synthesis and in vitro anti-proliferative capabilities of steroidal thiazole and indole derivatives

Derivatives (1–15) of steroidal and indole class were synthesized using different strategies. These compounds were characterized by ¹H NMR spectroscopy and EI-MS, respectively. The synthetic derivatives were examined for their cytotoxic effects on human adenocarcinoma cells (HCT-116) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and morphometric analysis. The cytotoxic effects of all the compounds were observed after 48 h treatment and it was found that out of fifteen, four compounds 1, 2, 3, and 14 showed inhibitory action on the cancer cells. We have calculated the IC₅₀ values for compounds 1, 2, 3, and 14 which were 22.50 µg/mL, 55.65 µg/mL, 21.35 µg/mL and 58.50 µg/mL, respectively. The compounds 3 (IC₅₀ = 21.35 µg/mL) and 1 (IC₅₀ = 22.50 µg/mL) showed highest inhibitory activities as compared to compounds 2 (IC₅₀ = 55.65 µg/mL) and 14 (IC₅₀ = 58.50 µg/mL). These results suggested that steroidal thiazole and indole derivatives are potent lead molecules having strong anti-cancer proliferative capabilities.     

Synthesis,SAR and in vitro therapeutic potentials of thiazolidine-2,4-diones

Background

Thiazolidinedione is a pentacyclic moiety having five membered unsaturated ring system composed with carbon, oxygen, nitrogen and sulfur molecules at 1 and 3 position of the thiazole ring and widely found throughout nature in various form. They favourably alter concentration of the hormones secreted by adipocytes, particularly adiponectin. They also increase total body fat and have mixed effects on circulating lipids. Thiazolidinedione nucleus is present in numerous biological moieties and has different pharmacological activities likes, e.g. antimalarial, antimicrobial, antimycobacterial, anticonvulsant, antiviral, anticancer, anti-inflammatory, antioxidant, anti-HIV (human immunodeficiency virus) and antituberculosis.

Results and discussion

The synthesized compounds were screened for their in vitro antimicrobial potential against Gram (positive and negative) bacterial and fungal strains by tube dilution technique. In this series, compound 10 exhibited significant antimicrobial activity against B. subtilis and S. aureus with MIC?=?4.2?×?10^?2 µM/ml, compound 15 showed significant activity against K. pneumonia with MIC?=?2.60?×?10^?2 µM/ml and compound 4 displayed potent antibacterial activity against E. coli with MIC?=?4.5?×?10^?2 µM/ml. Compound 10 had most potent antifungal activity against C. albicans and A. niger with MIC?=?4.2?×?10^?2 µM/ml. Compounds 12 and 15 were found as most active antidiabetic agents having IC₅₀?=?27.63 μg/ml and 22.35 μg/ml, respectively, using DPPH assay. Antioxidant activity results indicated that compounds 3 and 9 displayed good antioxidant agent with IC₅₀?=?29.04 μg/ml and 27.66 μg/ml respectively, using α amylase assay.

Conclusion

All the synthesized derivatives exhibited good antimicrobial, antidiabetic and antioxidant activities using specific methods then compared with mentioned standard drugs. Especially, compounds 3, 4, 9, 10, 12 and 15 displayed highest activity. Structure activity relationship demonstrated that presence of electron withdrawing group (o-NO₂, p-Cl, p-Br) enhanced the antibacterial activity against E. coli as well as increased the antioxidant activity while the presence of electron releasing group (o/p-OCH₃, 3,4,5-trimethoxy) enhanced the antibacterial activity against S. aureus, B. subtilis, S. typhi, K. pneumonia, C. albicans and A. niger as well as the antidiabetic activity.

     

Novel quinazolin-4(3H)-one derivatives containing a 1,3,4-oxadiazole thioether moiety as potential bactericides and fungicides: Design,synthesis, characterization and 3D-QSAR analysis

A series of quinazolin-4(3H)-one derivatives containing a 1,3,4-oxadiazole thioether moiety were designed, synthesized and evaluated for their biological activities against phytopathogenic microorganisms. Antimicrobial bioassays in vitro indicated that most of the target compounds exhibited more significant antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) than the agricultural bactericide thiadiazole-copper. A comparative molecular similarity index analysis (CoMSIA) model with cross-validated q² and non-cross-validated r² values of 0.561 and 0.882 was generated to investigate the structure-activity relationships of title compounds against Xoo. Title compound 6w, which was rationally designed under the guidance of obtained CoMSIA model, exhibited the excellent anti-Xoo effect in vitro with an EC₅₀ value of 29.10 μg/mL, which is approximately 3-folds more effective than thiadiazole-copper (113.93 μg/mL). In addition, compound 6i demonstrated the impressive antifungal effects against Rhizoctonia solani (Rs) and Fusarium graminearum (Fg) in vitro, with the corresponding EC₅₀ values of 11.01 μg/mL and 36.00 μg/mL, which is obviously better than the agricultural fungicide hymexazol (76.74 μg/mL and 56.19 μg/mL, respectively). The above researches indicate that quinazolin-4(3H)-one derivatives containing a 1,3,4-oxadiazole thioether moiety could be further studied as template molecules of novel agricultural microbicides.     

Design,synthesis, characterization,and antimicrobial evaluation of some new pyridine and chromene derivatives containing Lidocaine analogue

In an attempt to find a new class of antimicrobial agents, a series 2-pyridinone and 2-iminochromene derivatives containing Lidocaine analogue were designed and synthesized. The 2-pyridinone derivatives (3), (4), and (6) were obtained through the cyclocondensation of 2-cyano-N-(2,6-dimethylphenyl)-acetamide (2) with 1,3-dicarbonyl compounds and/or ternary condensation of (2), aromatic aldehyde, and malononitrile. Also, a series of 2-iminochromene derivatives (7–9) were synthesized through the condensation reaction of cyanoacetamide derivative (2) with salicylaldehyde derivatives. The structure of the new compounds were confirmed based on elemental analysis and spectral data. These compounds were screened for their antibacterial and antifungal activity The minimal inhibitory concentration (MIC) (µg/mL) of the most active (4), (5b), and (8) derivatives were determined. The MIC values between 7.81 and 31.26 µg/mL against bacterial species for (8) derivative, and upon comparison to tetracycline exhibited a positive control MIC (31.26–62.6 µg/mL). Besides, the activity against C. albicans (ATCC 1023) showed a MIC value of 15.63 µg/mL, which is similar to that of Amphotericin B.