Novel isoniazid embedded triazole derivatives: Synthesis, antitubercular and antimicrobial activity evaluation

Patil, Pravin; Kasare, Sanghratna L.; Haval, Nitin B.; Khedkar, Vijay M.; Dixit, Prashant P.; Rekha, Estharla Madhu; Sriram, Dharmarajan; Haval, Kishan P.

doi:10.1016/j.bmcl.2020.127434

Cited by 44 publications

(12 citation statements)

References 33 publications

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“…Inhibited protein formation has also been suggested in a proteomics study of Mtb treated with ciprofloxacin [135], as well as a metabolomics study of M. smegmatis treated with ciprofloxacin [48]. Disruption of protein synthesis has also been reported in studies investigating the response of Mtb to pretomanid, streptomycin, EMB, RIF, PZA, and INH [95,[136][137][138]. The inhibited protein synthesis observed would in turn disrupt the functionality of membrane proteins, subsequently inhibiting nutrient uptake as well as fatty acid transport to the cell wall [42].…”

Section: Discussionmentioning

confidence: 88%

Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics

et al. 2021

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In the interest of developing more effective and safer anti-tuberculosis drugs, we used a GCxGC-TOF-MS metabolomics research approach to investigate and compare the metabolic profiles of Mtb in the presence and absence of ciprofloxacin. The metabolites that best describe the differences between the compared groups were identified as markers characterizing the changes induced by ciprofloxacin. Malic acid was ranked as the most significantly altered metabolite marker induced by ciprofloxacin, indicative of an inhibition of the tricarboxylic acid (TCA) and glyoxylate cycle of Mtb. The altered fatty acid, myo-inositol, and triacylglycerol metabolism seen in this group supports previous observations of ciprofloxacin action on the Mtb cell wall. Furthermore, the altered pentose phosphate intermediates, glycerol metabolism markers, glucose accumulation, as well as the reduction in the glucogenic amino acids specifically, indicate a flux toward DNA (as well as cell wall) repair, also supporting previous findings of DNA damage caused by ciprofloxacin. This study further provides insights useful for designing network whole-system strategies for the identification of possible modes of action of various drugs and possibly adaptations by Mtb resulting in resistance.

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Section: Discussionmentioning

confidence: 88%

Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics

et al. 2021

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“…Moreover, several drugs on the market, such as rufinamide (anticonvulsant), cetirizine (antibiotic), and tazobactam (antibacterial agent) have inserted a 1,2,3 triazole core into their framework [24] (Figure 1). In the literature, there are numerous 1,2,3-triazoles tethered to bioactive heterocyclic moieties, such as (Figure 2A-D), that have been documented as promising antitubercular agents [25][26][27][28][29][30][31]. In particular, the 1,4-disubstituted 1,2,3-triazole derivatives were identified and proven to have high efficacy against Mycobacterium tuberculosis.…”

Section: Introductionmentioning

confidence: 99%

“…The importance of the phenoxy methyl moiety in the development of the new candidate with significant antimycobacterium activity is represented by the lead structure (Figure 3B), which exerts its activity through inhibition of the enoyl-acyl carrier protein reductase InhA enzyme, IC50 = 0.38 µM [33]. In the literature, there are numerous 1,2,3-triazoles tethered to bioactive heterocyclic moieties, such as (Figure 2A-D), that have been documented as promising antitubercular agents [25][26][27][28][29][30][31]. In particular, the 1,4-disubstituted 1,2,3-triazole derivatives were identified and proven to have high efficacy against Mycobacterium tuberculosis.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis and Molecular Docking of Novel Acetophenone-1,2,3-Triazoles Containing Compounds as Potent Enoyl-Acyl Carrier Protein Reductase (InhA) Inhibitors

et al. 2022

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New medications are desperately needed to combat rising drug resistance among tuberculosis (TB) patients. New agents should ideally work through unique targets to avoid being hampered by preexisting clinical resistance to existing treatments. The enoyl-acyl carrier protein reductase InhA of M. tuberculosis is one of the most crucial targets since it is a promising target that has undergone extensive research for anti-tuberculosis drug development. A well-known scaffold for a variety of biological activities, including antitubercular activity, is the molecular linkage of a1,2,3-triazole with an acetamide group. As a result, in the current study, which was aided by ligand-based molecular modeling investigations, 1,2,3-triazolesweredesigned and synthesized adopting the CuAAC aided cycloaddition of 1-(4-(prop-2-yn-1-yloxy)phenyl)ethanone with appropriate acetamide azides. Standard spectroscopic methods were used to characterize the newly synthesized compounds. In vitro testing of the proposed compounds against the InhA enzyme was performed. All the synthesized inhibitors completely inhibited the InhA enzyme at a concentration of 10 µM that exceeded Rifampicin in terms of activity. Compounds 9, 10, and 14 were the most promising InhA inhibitors, with IC50 values of 0.005, 0.008, and 0.002 µM, respectively. To promote antitubercular action and investigate the binding manner of the screened compounds with the target InhA enzyme’s binding site, a molecular docking study was conducted.

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“…It was observed that in recent years, isoniazid and its derivatives have received attention and are being widely studied. The derivatives of isoniazid are evaluated for their various biological activities, such as anti-inflammatory [8], anticancer [9,10], antimicrobial [11][12][13], anti-tubercular [2,11,[14][15][16][17], and in the treatment of Alzheimer's disease [18].…”

Section: Introductionmentioning

confidence: 99%

Microwave-Assisted Synthesis of Schiff Bases of Isoniazid and Evaluation of Their Anti-Proliferative and Antibacterial Activities

Al-Hiyari

Shakya

Naik

et al. 2021

Molbank

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Three new Schiff bases of isoniazid were synthesized using microwave-assisted synthesis and conventional condensation with aromatic aldehydes. Synthesized compounds were characterized using elemental analysis, IR, NMR, and Mass spectroscopy. Synthesized compounds were evaluated for antiproliferative activity against MCF-7 cell line. The IC50 values were from 125 to 276 µM. The compounds were also evaluated for antibacterial activity against Staphylococcus aureus and Escherichia coli. Results showed that the synthesized compounds produce significant antibacterial activity in vitro. Inhibition of compounds ranged from 13 to 18 mm.

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Novel isoniazid embedded triazole derivatives: Synthesis, antitubercular and antimicrobial activity evaluation

Cited by 44 publications

References 33 publications

Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics

Elucidating the Antimycobacterial Mechanism of Action of Ciprofloxacin Using Metabolomics

Design, Synthesis and Molecular Docking of Novel Acetophenone-1,2,3-Triazoles Containing Compounds as Potent Enoyl-Acyl Carrier Protein Reductase (InhA) Inhibitors

Microwave-Assisted Synthesis of Schiff Bases of Isoniazid and Evaluation of Their Anti-Proliferative and Antibacterial Activities

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