CAN catalyzed one-pot synthesis and docking study of some novel substituted imidazole coupled 1,2,4-triazole-5-carboxylic acids as antifungal agents

The present work describes a facile,one-pot three component synthesis of a series of 3-[(4,5-diphenyl-2-substituted aryl/heteryl)-1H-imidazol-1-yl]-1H-1,2,4-triazole-5-carboxylic acid derivatives M(1-15).Benzil,aromatic aldehydes and 3-amino-l,2,4-triazole-5-carboxylic acid was refluxed in ethanol using cerric ammonium nitrate(CAN) as a catalyst to give the title compounds in good yields.The compounds were evaluated for their in vitro antifungal and antibacterial activity.Compounds M1,M9,and M15 were found to be equipotent against Candida albicans when compared with fluconazole.Compounds M2.M5,and M14 showed higher activity against Streptococcus pneumoniae.Escherichia coli and Streptococcus pyogenes,respectively,compared with ampicillin.Docking study of the newly synthesized compounds was performed,and the results showed good binding mode in the active sites of C albicans enzyme cytochrome P450 lanosterol 14α-demethylase.The results of in vitro antifungal activity and docking study showed that synthesized compounds had potential antifungal activity and can be further optimized and developed as a lead compound.     

Design,synthesis and antiviral activities of chalcone derivatives containing pyrimidine

A series of chalcone derivatives (T1-T23) containing pyrimidine were synthesized, characterized, and assessed for their antiviral activity against tobacco mosaic virus (TMV) activities. Most target compounds displayed better antiviral activities against TMV than commercial ningnanmycin. Among them, the EC₅₀ value of curative activities of compounds T1, T7, T9 and T19 (219.2, 228.2, 279.9 and 234.9 μg/mL, respectively) were superior to that of ningnanmycin (320.1 μg/mL). In addtion, the EC₅₀ value of protective activities of compounds T5, T9, T19 and T23 (235.0, 220.0, 199.5 and 187.2 μg/mL, respectively) were superior to that of ningnanmycin (307.4 μg/mL). Then, the antiviral mechanism of T19 and TMV coat protein (TMV-CP) was preliminarily investigated by microscale thermophoresis (MST) and molecular docking technology. The results showed that T19 had a strong binding affinity for TMV coat protein, and its dissociation constant (K_d) was 0.00310 ± 0.000916 μM, which was superior to ningnanmycin(0.165 ± 0.0799 μM). This study suggests that chalcone derivatives containing pyrimidine could be used as novel antiviral agents for controlling the plant viruses.     

Synthesis of 5-{[(1Hbenzo[d]imidazol-2-yl)sulfonyl]methyl}-3-phenyl-4,5-dihydroisoxazole derivatives,invitro antibacterial and antioxidant studies along with their insilico analyses

Synthesis of a series of novel sulfone derivatives 6(a-u) possessing benzimidazoles and isoxazoline rings tailored in a single molecule 5(a-u) was done by reactions using 5-(bromomethyl)-3-phenyl-4,5-dihydroisoxazoles 3(a-u) and 5-{[(1H-benzo[d]imidazol-2-yl)thio]methyl}-3-phenyl-4,5-dihydroisoxazoles 4(a-u) molecules. The chemical structures of all the newly synthesized compounds were established by IR, ¹HNMR, ¹³CNMR and LCMS spectral data. The biological characteristics of the novel sulfone compounds, such as their antioxidant and antibacterial activity, were evaluated. Among the synthesized sulfones derivatives, compounds 6 g, 6b, and 6e demonstrated outstanding antibacterial activity while compounds 6b, 6c, 6i, 6j, and 6 k demonstrated higher antioxidant activity. Further insilico absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies of synthesized sulfones were studied which exhibited excellent intestinal absorption which is more than 80 %, and relatively moderate toxicity. Molecular docking studies confirmed the antibacterial and antioxidant potential which is comparable with the standard.     

Tris(hydrogensulfato) boron as a solid heterogeneous catalyst for the rapid synthesis of α,α’-benzylidene bis(4-hydroxycoumarin) derivatives

α, α’-Benzylidene bis（4-hydroxycoumarin） derivatives were readily prepared in a few minutes with good yields through the reaction of an aromatic aldehyde and 4-hydroxycoumarin in aqueous media in the presence of catalytic tris（hydrogensulfato） boron [B（HSO₄）₃].     

Design,synthesis, and biological evaluation of diarylpyrazole derivatives as antitumor agents targeting microtubules

A new series of novel diarylpyrazole derivatives as microtubule destabilizers were synthesized and evaluated for the anti-proliferative activities. Anti-proliferative assays were performed on the human cervix adenocarcinoma cell line (HeLa) and human gastric adenocarcinoma cell line (SGC-7901), and the compound 9s containing indole ring showed great anti-proliferative activity against HeLa cells with IC₅₀ value of 1.9 ± 0.11 μM. Further biological studies showed that 9s was able to inhibit tubulin polymerization, disrupt the cytoskeleton, block the cell cycle in the G2/M phase, and induce cell apoptosis in a concentration-dependent manner. In addition, the results of molecular docking studies showed that compound 9s could bind tightly to the colchicine binding site of tubulin through hydrogen bonding interaction. These preliminary results recommend that compound 9s is likely to be a microtubule destabilizer that deserves further investigation.     

Design,synthesis and in silico study of pyridine based 1,3,4-oxadiazole embedded hydrazinecarbothioamide derivatives as potent anti-tubercular agent

Development of novel, safe and effective drug candidates combating the emerging drug resistance has remained a major focus in the mainstream of anti-tuberculosis research. Here, we inspired to design and synthesize series of new pyridin-4-yl-1,3,4-oxadiazol-2-yl-thio-ethylidene-hydrazinecarbothioamide derivatives as potential anti-tubercular agents. The anti-tubercular bioactive assay demonstrated that the synthesized compounds exhibit potent anti-tubercular activity (MIC = 3.9–7.81 μg/mL) in comparison with reference drugs Rifampicin and Isoniazid.We employed pharmacophore probing approach for the identification of CYP51 as a possible drug target for the synthesized compounds. To understand the preferable binding mode, the synthesized molecules were docked onto the active site of Sterol 14 α-demethylases (CYP51) target. From the binding free energy of the docking results it was revealed that the compounds were effective CYP51 inhibitors and acts as antitubercular agent.     

Synthesis and antioxidant activities of flavonoids derivatives, troxerutin and 3’, 4’, 7-triacetoxyethoxyquercetin

Syntheses of two very important derivatives of quercetin,troxerutin and 3’,4’,7-triacetoxyethoxyquercetin were described.The latter was synthesized by highly selective esterification reaction in first time.The compounds were characterized by NMR,IR and Mass spectroscopy.Additionally,the antioxidant activities of the compounds were tested by means of improved pyrogallol autoxidation method.This was the first in using this method to test the antioxidant activities of these two compounds in vitro.The optimum system of pyorgallol autoxidation spectrophotometry was investigated and established according to the reaction rules.The assay indicated that these compounds showed noticeable antioxidant activities,and compound 2 was much more effective as a free radical scavenger than the compound 1 vitamin C was used as a reference material.     

Phytofabrication of silver nanoparticles from Limonia acidissima leaf extract and their antimicrobial,antioxidant and its anticancer prophecy

Green synthesis of nanoparticles by eco-friendly methods is a recent technique which draws the attention of researchers because of the reward over many conventional chemical methods. The present work focuses on aqueous Limonia acidissima leaf extract in synthesizing silver nanoparticles and its applications in a simple way. The silver nanoparticles formed were characterized by Infrared, Ultra violet-visible, X-ray diffraction, transmission electron microscopic, and atomic force microscopic techniques. The powder X-ray diffraction studies and transmission electron microscopic images reveal that the silver nanoparticles synthesized were approximately 10–40 nm and have a spherical structure. The nanoparticles were assayed for their antibacterial, antifungal and antioxidant activity. The antimicrobial studies for the silver nanoparticles show a maximum zone of inhibition of 8.8 mm for Bacillus subtilis bacteria and 8.5 mm for Candida albicans fungi at 3 and 1 μg/mL respectively. In-silico ADMET studies reveal that the toxicity, bioactivity, pharmacokinetics and drug-likeness properties of Limonia acidissima leaf extract is good. The molecular docking studies show that the microbial activity is high for Bacillus subtilis and Candida albicans showing the coincidence of the in silico and in vitro studies as expected. The free radical scavenging activity of nanoparticles is 80 for 100 μg/mL. The 50% of inhibition of silver nanoparticles against human breast cancer cell lines is 18 μg/mL. It is evident that silver nanoparticles would be helpful in treating cancer cell lines and have great perspectives in the biomedical sector.     

Green synthesis of bis-coumarin derivatives using Fe(SD)3 as a catalyst and investigation of their biological activities

A convenient, practical, green, and environmentally friendly method was developed for the synthesis of biscoumarins and corresponding tetrakis products from the reaction of 4-hydroxycoumarin and various aldehydes. The bis-coumarins were synthesized in high yield under mild reaction conditions. Products were obtained in the presence of in situ prepared Fe(SD)₃ [Iron(III) dodecyl sulfate] as a combined Lewis acid–surfactant catalyst (LASC) in water in short reaction times. Also, the antibacterial activity of compounds was screened against Pseudomonas aeruginosa and Escherichia coli as Gram-negative bacteria and Micrococcus luteus and Staphylococcus aureus as Gram-positive bacterial strains. Products 3g , 3k–l were most active than cefotaxime against E. coli and also compounds 3c and 3g were most active than cefotaxime against S. aureus.     

Design,synthesis and insecticidal activities of novel 1-substituted-5-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives

A series of novel 5-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives(6a–6n, 7a, 7b, and 8a-8f)were synthesised by placing the amide bond at the 4-position of the pyrazole ring. These derivatives differed from the structure of chlorantraniliprole analogues with the amide bond at the 5-position of the pyrazole ring. Preliminary bioassay results revealed that a few title compounds exhibited good insecticidal activities against lepidopteran pests, such as Plutella xylostella, Mythimna separate, Heliothis armigera, and Ostrinia nubilalis. Some title compounds also elicited broad-spectrum insecticidal activities against dipterous insects including Culex pipiens pallens after altering the amide position. Similar to pyrazole-5-carboxamide analogues, compounds 6b and 6e showed 100% insecticidal activity against P. xylostella, C. pipiens pallens, and M. separate at concentrations of 200, 2, and 200 mg/m L, respectively.This finding suggested that 5-(trifluoromethyl)-1H-pyrazole-4-carboxamide derivatives are potential alternative insecticides for management of agriculture pests.     

Design,synthesis and anti-diabetic activity of chromen-2-one derivatives

DPP-IV inhibitors have been immersed as promising pathway to treat Type 2 diabetes. Here we have reported designing of coumarin derivatives as DPP-IV inhibitors. Designed compounds have been studied for their binding with DPP-IV enzyme through molecular docking followed by synthesis. All synthesized compounds have been fully characterized and screened for DPP-IV inhibition activity. Two compounds showed very good inhibition at 10 μM concentration.     

Synthesis and studies of calcium channel blocking and antioxidant activities of novel 4-pyridinium and/or N-propargyl substituted 1,4-dihydropyridine derivatives

The novel 1,4-dihydropyridine derivatives containing the cationic pyridine moiety at the position 4, and the N-propargyl group as a substituent at position 1 of the 1,4-DHP cycle were designed, synthesised, and assessed in biological tests. Among all the novel compounds, the 4-(N-dodecyl) pyridinium group-containing compounds 11 (without the N-propargyl group) and 12 (with the N-propargyl group) demonstrated the highest calcium antagonistic properties against neuroblastoma SH-SY5Y (IC₅₀ about 5–14 μM) and the vascular smooth muscle A7r5 cell (IC₅₀ – 0.6–0.7 μM) lines, indicating that they predominantly target the L-type calcium channels. These compounds showed a slight total antioxidant activity. At concentrations close to those of L-type calcium channel blocking ones, compound 12 did not affect mitochondrial functioning; also, no toxicity was obtained in vivo. The N-propargyl group as a substituent at position 1 of the 1,4-DHP cycle did not essentially influence the compounds’ activity. The 4-(N-dodecyl) pyridinium moiety-containing compounds can be considered as prototype molecules for further chemical modifications and studies as cardioprotective/neuroprotective agents.     

Construction,molecular docking,antimicrobial and antioxidant activity of some novel 3-substitued indole derivatives using 3-Acetyl indole

This dissertation presents a method for the synthesis of substituted indoles bearing heterocyclic substituent in the 3- position. The route for the synthesis of the heterocyclic substituents indoles starts from the 3-acetyl indole nucleus. The reaction of 3-acetyl indole 1 with hydrazide compounds such as phenylhydrazine, hydrazine hydrate, and thio-semicarbazide, yields 3-(1-(2-phenylhydrazono) ethyl)-1H-indole 2, 3-(1-hydrazonoethyl)-1H-indole 6, and thiosemicarbazone 10, respectively. Thiophene-2-carboxaldeyde, isatine and 3-acetyl indole reacted with 3-(1-Hydrazonoethyl)-1H-indole 6. In the same way, 3-(1-(2-phenylhydrazono) ethyl)-1H-indole 2 reacted with thioglycollic acid, glycine and benzaldehyde. Thiosemicarbazone 10 reacted smoothly with acetic anhydride, piperidine, concentration of hydrochloric acid and thiophene-2-carboxaldeyde to provide the corresponding heterocycles. The reaction of 3-acetyl indole 1 with amine compounds such as p-nitroaniline formed Schiff base 15, which reacted with thioglycollic acid to give compound 16. 3-Acetyl indole 1 reacted with ethylene diamine to afford bis imine indole 17. The reports of the docking study revealed that the new compounds exhibit good antibacterial activity. The synthesized compounds screened in vitro for their antibacterial activity revealed remarkable inhibitory effects on the selected microorganisms. Besides, the antioxidant activity of some newly designed compounds has been investigated. The structures of the newly synthesized compounds are examined by spectral data (IR, ¹HNMR, ¹³C NMR and mass spectra).     

Synthesis,nematicidal activity and docking study of novel chromone derivatives containing substituted pyrazole

A series of chromone derivatives containing substituted pyrazole were designed and synthesized. Preliminary bioassays showed that most of the synthesized compounds exhibited good nematicidal activity in vivo against Meloidogyne incognita at 10 mg/L.     

Efficient synthesis of new azo-sulfonamide derivatives and investigation of their molecular docking and cytotoxicity results

The present study focused on the synthesis, introduction and investigation of the biological effects of sulfonamide-derived products as new azo-sulfonamides (samples 1–6). In this transformation, the amine sulfonamide is first converted to the corresponding diazonium salt, which is then attacked by a nucleophilic carbon of the aromatic ring in the playing medium. All products were obtained with reasonable yields and high purity. The structure of synthesized derivatives was determined using various analytical tools including FT-IR, ¹H NMR, ¹³C NMR and XRD spectroscopy, and the synthesized products were purified and identified. Biological properties of newly synthesized azo-compounds similar to SSZAD were also investigated. These compounds were tested in terms of biological effectiveness. The results of biochemical assays show that: the products have significant biological properties. MTT toxicity of compounds in breast cancer cells (MCF-7) for compounds 1–6 according to IC₅₀ compare to Vinblastine is Vin > 5 > 4 > 6 > 2 > 3 > 1. The biochemical results obtained were analyzed by molecular docking interaction studies and showed strong hydrogen bonding with the target receptor. The docking calculation has been invoked to reveal the type of interactions that synthesized compounds can establish with the residues forming the active sites of the target proteins, 1FDW the three higher scores molecules appears to be (6 > 1 > 2), 3FC2 (the three highest binding affinities are in the order of 1 > 3 > 6), and 5GWK (three highest binding affinities are 1 > 3 > 6). The results indicate the effective interaction of all products with the targets. The molecular dynamics simulation has been invoked to study the presence of a stable system of the interacting protein–ligand.     

BSA mediated Ag@Bi2S3 composites: synthesis,characterization, photodegradation of mixed dyes via metal-semiconductor interface,antimicrobial and antioxidant activities

Nowadays, the development of metal-metal sulfide interface semiconductors using green approach is best material for the photocatalytic and biological applications. Here, we provided for the first time, an environmentally friendly route to fabricate bovine serum albumin (BSA) assisted Ag@Bi₂S₃ composites through a metal-metal sulphide interface via a simple hydrothermal method for the evaluation of photochemical and biological applications. The synthesized composites were characterized by UV–vis DRS, PL, XRD, TEM, and N₂ adsorption-desorption isotherms. The UV–vis DRS and PL spectra show that the obtained nano-sized Ag@Bi₂S₃ composite displays enhanced visible-light absorption and a decreased fluorescence emission compared to that of Bi₂S₃ nanorods (NRs). The photocatalytic performances of the synthesized composites were evaluated by the degradation of the single (RhB and MB) and mixed dye (RhB+MB) under sunlight irradiation. The results indicated that the Ag@Bi₂S₃ composite exhibits superior photocatalytic activity (98.38%) than that of individual Ag NPs and Bi₂S₃ NRs due to the synergistic effect of Ag and Bi₂S₃ nanophases in the Ag@Bi₂S₃ composite, which results in an effective charge separation, fast electron transfer from Ag to Bi₂S₃, and a low recombination of photo-induced electron-hole pairs. The Ag@Bi₂S₃ composite also has good recycling stability up to 5 cycles and its mechanism also investigated. The evaluation of reactive species during the photocatalytic reaction was also carried out. Further, the effects of Bi₂S₃ and Ag NPs on the antimicrobial and antioxidant activity of the resultant Ag@Bi₂S₃ composite were also systematically investigated.     

Benzylation of β-dicarbonyl compounds and 4-hydroxycoumarin using TMSOTf catalyst: a simple, mild, and efficient method

The direct benzylation of 1,3-dicarbonyl compounds and 4-hydroxycoumarin with a wide variety of benzylic alcohols was achieved using trimethylsilyl trifluoromethanesulfonate as an efficient catalyst. The reaction proceeded under very mild conditions at room temperature providing the desired products in good to excellent yields.     

Synthesis,antimicrobial, and antioxidant activities of new pyridyl‐ and thiazolyl‐bearing carbohydrazides

A series of novel substituted (E)‐N′‐benzylidene‐4‐methyl‐2‐(2‐propylpyridin‐4‐yl)thiazole‐5‐carbohydrazide derivatives ( 6a‐l ) have been synthesized by following the multistep synthetic route starting from prothionamide. The resulting compounds were characterized via ¹H, ¹³C NMR, and HRMS spectral data. The synthesized carbohydrazides were evaluated for their in vitro antimicrobial and antioxidant activities. Tested molecules have displayed moderate to good growth inhibition activity. Among the screened compounds, 6b , 6e , 6j, and 6k are found to be the more promising antimicrobial agents. A 2,2‐diphenyl‐1‐picrylhydrazyl assay was used to test the antioxidant activity of the carbohydrazides. The carbohydrazide derivatives 6b and 6i have shown better free‐radical scavenging ability than the other investigated compounds.