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In search of new active molecules, a small focused library of new 1,2,3-triazoles derived from naphthols were efficiently prepared via the click chemistry approach. The synthesized triazole derivatives were evaluated for their antifungal, antioxidant and antitubercular activities. Furthermore, to rationalize the observed biological activity data, the molecular docking study has also been carried out against the active site of cytochrome P450 lanosterol 14α-demethylase of C. albicans to understand the binding affinity and binding interactions of enzyme and synthesized derivatives, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of the in vitro and In Silico study suggest that the 1,2,3-triazole derivatives may possess the ideal structural requirements for the further development of novel therapeutic agents. [ABSTRACT FROM AUTHOR]

Oxidative stress causes an imbalance between formation and accumulation of reactive oxygen species in cells and tissue, leading to various chronic and degenerative illnesses, viz. aging, cataract, cancer, rheumatoid arthritis, autoimmune disorders, and cardiovascular and neurodegenerative diseases. In this study, we have screened a library of bis-1,2,3-triazolyl-N-phenylacetamides (3a–z) for their in vitro antioxidant activity via 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. A detailed structure activity relationship study was undertaken to identify the key substitution contributing to the antioxidant activity followed by molecular docking study against enzyme myeloperoxidase (MPO). Myeloperoxidase is a heterodimeric, cationic, and glycosylated heme enzyme, which gets released under increased oxidative stress producing neutrophil oxidant, hypochlorous acid having the capacity to modify various biomolecules by chlorination and/or oxidation of sulfhydryl groups in proteins causing their inactivation and promoting tissue damage. The in silico binding affinity study could shed light on the binding modes of these molecules and further identify the thermodynamic interactions with active site residues governing the binding affinity. This in silico study could provide a platform for structure-based optimization of bis-1,2,3-triazolyl-N-phenylacetamides as potential modulators of pro-oxidative tissue injury pertubated by the MPO/H2O2/HOCl/HOBr system. Here, the ultimate study results illustrated that most of the derivatives were more active than standard antioxidant agent. Hence, this study also serves a significant contribution in the discovery of potent antioxidants in future research. [ABSTRACT FROM AUTHOR]

A simple and efficient protocol has been developed for the synthesis of new1,2,3-triazole-2,3-dihydroquinazolin-4[1H]-one (DHQ) conjugates(6a−j) via ultrasound-assisted, solvent-free ionic liquid [HDBU][HSO4]-catalyzed reaction in good to excellent yields. This non-conventional, ultrasound-assisted route has taken the reactions over the conventional reflux method to provide good to excellent yields of the corresponding products (6a−j) in a very short time. In addition, mild reaction conditions, tolerance to functionalized substrates, ease of product isolation, prevention of its over oxidation and reusability of catalyst [HDBU][HSO4] are some key striking features of the methodology. The newly synthesized derivatives (6a−j) were screened for antioxidant activity using 1,1-diphenyl-2-picryl hydrazyl (DPPH) assay and are found to be a potent scavenger. The compounds 6b, 6c, 6d, 6e and 6i showed significant antioxidant activity. Molecular docking studies showed significant binding affinity in the active site of myeloperoxidase (MPO) enzyme and hence scavenged by inhibition of MPO. In silico ADMET and pharmacokinetic studies of the conjugates are very promising; a cumulative body of evidence suggests their medicinal value as a potential orally active drug candidate. [ABSTRACT FROM AUTHOR]

In the current experimental study, we have synthesised new monocarbonyl curcumin analogues bearing propargyl ether moiety in their structure and evaluated for in vitro antifungal and radical scavenging activity. The antifungal activity was carried out against five human pathogenic fungal strains such as Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger and Cryptococcus neoformans. Most of the curcumin analogues displayed excellent to moderate fungicidal activity when compared with standard drug Miconazole. Also, synthesised analogues exhibited potential radical scavenging activity as compared with standard antioxidant Butylated hydroxyl toluene (BHT). Based on biological data, structure-activity relationship (SAR) were also discussed. Furthermore, in silico computational study was carried out to know binding interactions of synthesised analogues in the active sites of enzyme sterol 14α-demethylase (CYP51). [ABSTRACT FROM AUTHOR]

Curcumin is an active component of turmeric that has poor solubility, stability and bioavailability. The monocarbonyl curcumin analogues were modified from curcumin to achieve more stable and active compounds as compared to curcumin. Therefore, we have designed and synthesized a library of 18 compounds of α,α'-bis(1H-1,2,3-triazol-5-ylmethylene) ketones (8a–o) and evaluated them for their in vitro antitubercular and antioxidant activities against their respective strains. Results of biological activities reveal that some of the compounds from the series showed good antitubercular as well as antioxidant activities. The compound 8l was found as the most active antitubercular agent with MIC value 3.125 µg/mL, against Mtb H37Rv. Moreover, the compounds, 8c, 8d, 8e and 8g, also showed potent antitubercular activity. The compounds 8e and 8m displayed potent antioxidant activities with IC50 values 15.60 and 15.49 µg/mL, respectively. In support of the bioactivities, in silico ADME properties' prediction has also been carried out in this study. [ABSTRACT FROM AUTHOR]

Herein, a fast and convenient protocol for the synthesis of new isoniazid fused chromeno[4,3-b]quinolin was achieved through biomimetic catalysis by cyclodextrin in the water at 60–65 °C. The present investigation involves attractive characteristics such as the use of water as the reaction medium, one-pot conditions, short reaction periods, easy work-up/purification and reduced waste production. This method provides a green route for the synthesis of targeted scaffolds and also a wide substrate scope for several substituted aldehydes to provide good yields of the corresponding products. Furthermore, the catalyst can be easily recovered by simple filtration and reused several times without any substantial loss in activity. Our study also discloses the antimicrobial screening of new chromeno[4,3-b]quinolin-isonicotinamides against four bacterial and three fungal strains. [ABSTRACT FROM AUTHOR]

An efficient ultrasound-promoted one-pot three-component synthesis of a series of new 1,2,3-triazole-linked tetrahydrobenzo[b]pyran derivatives as antifungal and antioxidant agents using NaHCO3 has been described for the first time. The bioassay result indicates that the compounds 7b, 7c, 7i and 7j displayed excellent antifungal activity with lower MIC = 12.5 µg/mL than the reference drug miconazole. Most of the compounds from the series showed promising antioxidant activity with lower IC50 values in the range 12.47 ± 0.60–16.49 ± 0.44 µg/mL in comparison with butylated hydroxy toluene (BHT). Molecular docking studies revealed that most of the newly synthesized compounds showed excellent binding affinity with the potential target sterol 14α-demethylase (CYP51). Moreover, in silico adsorption, distribution, metabolism and excretion (ADME) study shows that the derivatives may possess drug like properties for further development of newer therapeutic agents. [ABSTRACT FROM AUTHOR]

Abstract: An efficient, green, high yielding, and quick method for the synthesis of N-substituted decahydroacridine-1,8-diones was achieved by multicomponent reaction between various aromatic aldehydes (1a-q), dimedone (2), and various aromatic amines (2a-d) using ChCl:Urea deep eutectic solvent as a recyclable organocatalyst and medium. The reaction conditions are relatively mild and do not require additional metals, acid catalysts, or organic solvents. The mild reaction conditions, experimental simplicity, straightforward purification procedures, excellent yields with short reaction times, as well as the application of green chemistry principles, are the advantages of this methodology. This simple ammonium deep eutectic solvent, easily synthesized from choline chloride and urea, is relatively inexpensive and biodegradable, making it applicable for industrial use. The deep eutectic solvent was easily separated and reused without loss of activity, and thus provides a good alternative. The synthesized 10-(substituted phenyl)-9-(substitutedphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine-1,8 (2H,5H)-diones (4a-l) were screened for their in vitro antimicrobial activity against four bacterial Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and three fungal strains (Candida albicans, Aspergillus niger and Aspergillus flavus). Among them, the 9-(N,N-Dimethylphenyl)-3,3,6,6-tetramethyl-10-(3-pyridyl)-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione (4f), 10-(4-Bromophenyl)-9-(3-hydroxy-4-methoxyphenyl)-3,3,6,6-tetramethyl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione (4i) and 9-(4-Nitrophenyl)-3,3,6,6-tetramethyl-10-phenyl-3,4,6,7,9,10-hexahydroacridine-1,8(2H,5H)-dione (4k) show good antimicrobial activity.Graphical Abstract: [ABSTRACT FROM AUTHOR]

Abstract: The synthesis of a new series of triazole-biscoumarin conjugates by using a molecular hybridization approach is described. The newly synthesized compounds 6a-k were evaluated for their in vitro antitubercular activity against active and dormant Mtb H37Ra and anti-oxidant activity against DPPH radical scavenging. Molecular docking simulations for the antitubercular activity showed that the conjugates 6a-k bind in the pocket of the DprE1 enzyme. Most of the conjugates displayed good antitubercular activity against both the active and dormant Mtb H37Ra strain. The compound 6h displayed very good antitubercular activity against dormant Mtb H37Ra with an IC50 value of 1.44 μg/mL. Most of the synthesized conjugates exhibit excellent anti-oxidant activity with an IC50 of less than the standard BHT. Compound 6b is the most active among all the conjugates with an IC50 value of 08.17 ± 0.11 μg/mL. The molecular docking study shows good agreement between the observed antitubercular activity and the binding affinity.Graphical Abstract: [ABSTRACT FROM AUTHOR]

Abstract: Simple and green synthetic procedures constitute an important goal in organic synthesis. The combination of multicomponent reactions (MCRs) and unconventional solvents has become a new research direction, which enables simultaneous growth of both MCRs and green solvents toward ideal organic synthesis. In this paper, we have summarized recent results of MCRs obtained in unconventional media using water and β-cyclodextrin, as supramolecular catalyst, for the synthesis of pyrano[2,3-d]-pyrimidinone (4a-q) derivatives. The compounds were evaluated for their in vitro antimicrobial activity. Among the synthesized compounds, compounds 4h, 4m and 4p exhibited higher antimicrobial activity than ciprofloxacin used as the reference drug. Most of the synthesized compounds have good to excellent antimicrobial activity. Furthermore, \ molecular docking study was performed to help understand binding interactions of the most active analogs with C30 carotenoid dehydrosqualene synthase enzyme.Graphical Abstract: [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase-IV (DPP-IV) inhibitors are promising antidiabetic agents. Currently, several DPP-IV inhibitors have been approved for therapeutic use in diabetes mellitus. Receptor-dependent 4D-QSAR is comparatively a new approach which uses molecular dynamics simulations to generate conformational ensemble profiles of compounds representing a dynamic state of compounds at a target’s binding site. This work describes a receptor-dependent 4D-QSAR study on triazolopiperazine derivatives. QSARINS multiple linear regression method was adopted to generate 4D-QSAR models. A model with 9 variables was found to have better predictive accuracy with R2=0.692, Q2 (leave-one-out) = 0.592 and R2 predicted = 0.597. The location of these 9 variables at the binding site of DPP-IV revealed the importance of the residues Val711, Tyr662, Tyr666, Val202, Asp200 and Thr199 in making critical interactions with DPP-IV inhibitors. The study of these critical interactions revealed the structural features required in DPP-IV inhibitors. Thus, in this study the importance of a halogen substituent on a phenyl ring, the extent of substitution on the triazolopiperazine ring, the presence of an ionizable amino group and the presence of a hydrophobic substituent that can bind deeper in binding pocket of DPP-IV were revealed. [ABSTRACT FROM AUTHOR]

To fulfil the development goals towards the synthesis of innovative, potent and highly effective antimicrobial and antimycobacterial agents, a set of benzene sulfonamide pyrazole thio-oxadiazole derivatives (6a-6l) have been synthesized by the reaction of 4-[5-(3-fluoro-4-methoxyphenyl)-3-(5-mercapto-1,3,4-oxadiazol-2-yl)-1H-pyrazol-1-yl]benzenesulfonamide with alkyl/aryl halides, identified by IR, NMR (1H, 13C, 19F) and MS data. Composed compounds were examined for their antimicrobial and antitubercular activity. Antibacterial activity of compounds 6c, 6d, 6j and 6l was found promising against E. coli, P. Aeruginosa, S. Aureus and S. Pyogenes as compared to standard ampicillin. Compounds 6d, 6e, 6g, 6h and 6i were found active against tubercular strain H37Rv. Molecular docking studies against mycobacterium tuberculosis β-ketoacyl-acyl carrier protein synthase A (Kas-A) was carried out which suggests a possible mode of inhibition for this target protein and the potential of synthesized compounds as antitubercular agents. [ABSTRACT FROM AUTHOR]

The work reports ultrasound-mediated greener synthesis of 11 novel 3-(4-(4-chlorophenyl)-6-(substituted phenyl/heteryl)pyrimidin-2-ylimino)indolin-2-one (7a-7k) derivatives. The synthesized derivatives were evaluated for their in vitro anticancer activity against a panel of selected human cancer cell lines of breast (MCF-7), cervix (HeLa), prostate (PC-3) and lung (A-549). Among the tested compounds, 7b exhibited most promising in vitro anticancer activity against HeLa, PC-3 and A-549 with GI50 value 15.38, 19.67 and 4.37 µM, respectively. The compounds (7a-7k) were also screened for induction of apoptosis and morphological changes in cancer cells at their GI50 concentration. The treatment of HeLa, PC-3 and A549 cancer cells with 7b and treatment of MCF-7 cancer cells with 7h showed apoptosis and morphological changes such as cell shrinkage, cell wall deformation and reduced number of viable cells. The compound 7b has shown almost 5.00 times more selectivity for PC-3 cancer cell lines in comparison to the RWPE-1 normal prostate epithelial cells. Molecular docking study has been carried out, which replicates results of biological activity in cases of initial hits 7b, 7c and 7d, suggesting that these compounds have a potential to become lead molecules in the drug discovery process. In silico ADMET study was performed for predicting pharmacokinetic properties and toxicity profile of the synthesized compounds and expressed good oral drug-like behaviour. An in vivo acute oral toxicity study was performed using Swiss albino mice for the most active compounds 7b and 7c, and results indicate that the compounds are non-toxic in nature. [ABSTRACT FROM AUTHOR]

A novel series of isoxazole clubbed 1,3,4-oxadiazole derivatives have been synthesized by reaction of 5-(3-fluoro-4-methoxyphenyl) isoxazole-3-carbohydrazide with different substituted benzoic/pyridinyl/indolyl acids in phosphorous oxychloride, characterized by IR, 1H NMR, 13C NMR, MS analytical data and evaluated for their antimicrobial as well as antitubercular activity. Antibacterial activity of compounds 5e, 5g, 5h, 5j and 5l were found to be good against E. coli, P. aeruginosa, S. aureus and S. pyogenes as compared to standard Ampicillin. Compound 5b and 5i were found to be active antitubercular agents against M. tuberculosis H37Rv. Antibacterial and antitubercular activity was supported by molecular docking to gain insights of the mode of inhibition of MurD ligase enzyme. [ABSTRACT FROM AUTHOR]

Ceric ammonium nitrate (CAN) is used as an efficient catalyst for the synthesis of 2,4,5-triaryl-1H-imidazoles via condensation of benzoin/benzil, ammonium acetate, and aromatic aldehydes. The easy work-up, higher yields and shorter reaction time are the advantages of the method presented here. [ABSTRACT FROM AUTHOR]