Search

In search of new active molecules, a small focused library of 1,2,3-triazoles based 2,4-thiazolidinedione derivatives has been efficiently prepared via the click chemistry approach. Several derivatives were exhibited excellent anti-inflammatory activity compared to the standard drug. Further, the synthesized compounds were found to have potential antioxidant activity. Furthermore, to rationalize the observed biological activity data, the molecular docking study has also been carried out against the active site of inflammation enzyme PPARγ, 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 triazole incorporated 2,4-thiazolidinedione derivatives may possess the ideal structural requirements for the further development of novel therapeutic agents. [ABSTRACT FROM AUTHOR]

A series of new benzimidazole incorporated 3,5-bis (arylidene)-4-piperidones were synthesized by using aryl aldehydes, piperidinone, 2-(chloromethyl)-benzimidazole and DBU acetate [DBUH][OAc] act as a catalyst under solvent free condition in excellent yields. The synthesized compounds were screened for their in vitro antimycobacterial activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. The compounds 4a, 4b, 4e, 4i, 4k and 4l are highly potent against both the strains. Most of the active compounds are non-cytotoxic against MCF-7, A549, HCT 116 and THP-1 cell lines. Furthermore, a molecular docking study of these compounds was carried out to investigate their binding pattern with the target, active site of mycobacterial enoyl-acyl carrier protein reductase (Inh A). Therefore, these compounds can be subjected for further optimization and drug development which could give promising chemical leads for treatment of TB. [ABSTRACT FROM AUTHOR]

An approach toward the synthesis of novel conjugates of 3,5-bis (arylidene)-4-piperidones (DAP) pharmacophore with amide-linkage has been developed via one-pot multicomponent reaction of aryl aldehydes, piperidinone and 2-chloro-N-phenylacetamide using [Et3NH][HSO4] as a catalyst/medium. Both substitutions on arylidene rings and piperidinone nitrogen (substituted 2-chloro-N-phenylacetamide) were varied. The synthesized conjugates were evaluated for their in vitro antitubercular activity against M. tuberculosis H37Ra (MTB) and M. bovis BCG strains. Among the series, compounds 4f, 4g, 4i and 4j showed remarkable broad spectrum antitubercular activity with low IC50 values. Furthermore, computer docking simulations, for the most active conjugates were performed with the active site of mycobacterial enoyl-acyl carrier protein reductase (InhA) support the antitubercular activity. Lower cytotoxicity, high potency and promising activity against MTB and M. Bovis BCG suggest that amide linked DAP could serve as good leads for further modifications and development. [ABSTRACT FROM AUTHOR]

In search of new active molecules, a small focused library of tetrazoloquinoline-based 1,2,3-triazoles has been efficiently prepared via click chemistry approach. Several derivatives were found to be exhibiting promising antimicrobial and antioxidant activity characterized by their lower minimum inhibitory concentration values. All the synthesized compounds exhibited excellent antibacterial activity against Gram negative bacteria E. coli and F. devorans and antifungal activity against C. albicans and A. niger. Further, these compounds were tested for their antitubercular activity against dormant MTB H37Ra and dormant M. bovis BCG using XRMA assay protocol and showed no significant activity. Also, the synthesized compounds were found to have potential antioxidant activity with IC50 range = 12.48–50.20 μg/mL. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against the active site of fungal C. albicans enzyme P450 cytochrome lanosterol 14α-demethylase, 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 triazole-incorporated tetrazoloquinolines may possess the ideal structural requirements for further development of novel therapeutic agents. [ABSTRACT FROM AUTHOR]

A series of new 1,2,3-triazolyl chalcones were efficiently synthesized and screened for in vitro antifungal activity against five different fungal strains such as Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger and Cryptococcus neoformans. All the synthesized chalcones displayed potential antifungal activity against most of the tested fungal strains. Especially, compounds 9b, 9c, 9d and 9g are the most active chalcones and displayed excellent MIC values as compared to standard antifungal drug Miconazole. Based on the structural similarity to known triazole inhibitors of sterol 14α-demethylase (CYP51), molecular docking study was performed to gauze the binding affinity of these chalcones and gains an insight into the plausible mechanism of antifungal action. The synthesized chalcones were also evaluated for in vitro antioxidant activity. All compounds exhibited moderate to excellent antioxidant activity, particularly compounds 9e, 9f, 9g and 9h exhibited excellent antioxidant activity in comparison with standard butylated hydroxytoluene (BHT). Furthermore, the synthesized chalcones were analyzed for ADME properties and showed the potential to build up as good oral drug candidates. [ABSTRACT FROM AUTHOR]

A series of quinoline incorporated monocarbonyl curcumin analogues was efficiently synthesized using [HDBU][HSO 4 ] as catalyst via Knoevenagel type condensation and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Ra (MTB) and Mycobacterium bovis BCG in dormant state. The analogues 3e , 3h , 4a and 4e exhibited very good antitubercular activity. The antiproliferative activity of the analogues against MCF-7, A549 and HCT-116 cell lines was evaluated using modified MTT assay and these compounds were found to be non-cytotoxic. Molecular docking study has been carried out against M. tuberculosis pantothenate synthetase (MTB PS) enzyme in an effort to enhance the understanding of their action as antitubercular agents. The potency, low cytotoxicity and selectivity of these analogues support them as valid leads for further optimization. [ABSTRACT FROM AUTHOR]

A library of 1,2,3-triazoles efficiently prepared via click chemistry and evaluated for their antifungal, antitubercular, antioxidant, cytotoxicity, molecular docking and ADME prediction. [ABSTRACT FROM AUTHOR]

The one-pot three-component syntheses of new N-sulfonamide-thiazolidin-4-one derivatives were carried out in excellent yield using [HDBU][HSO4] as an ionic liquid under solvent-free conditions. The newly synthesized compounds were screened against fungal strains and a number of compounds were seen to display excellent antifungal activity. In addition, the synthesized compounds were screened for their scavenging activity of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and showed very good antioxidant activity. Finally, theoretical predictions derived from molecular docking studies against the potential target sterol 14α-demethylase (CYP51) helped establish a link between the observed biological activity and the binding affinity, thereby providing insights into the specific bonding and non-bonding interactions governing the activity. [ABSTRACT FROM AUTHOR]

In search of new active molecules against Mycobacterium tuberculosis ( MTB ) H37Ra and M. bovis BCG , a small focused library of benzothiazinone based 1,2,3-triazoles has been efficiently prepared via click chemistry approach. Several derivatives were found to be promising inhibitors of MTB and M. bovis BCG characterized by lower MIC values (27.34–29.37 μg/mL). Among all the synthesized compounds, 6c and 6e is the most active compound against MTB and M. bovis BCG . The compounds were further tested for anti-proliferative activity against HeLa, A549 and A431 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antioxidant activity with IC 50 range = 14.14–47.11 μg/mL. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target MTB DprE1 , 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 triazole incorporated benzothiazinone may possess the ideal structural requirements for further development of novel therapeutic agents. [ABSTRACT FROM AUTHOR]