Synthesis of isoniazid analogs with promising antituberculosis activity and bioavailability: Biological evaluation and computational studies

Gavadia, Renu; Rasgania, Jyoti; Varma-Basil, Mandira; Chauhan, Varsha; Kumar, Sanjay; Jakhar, Komal

doi:10.1016/j.molstruc.2023.135325

Cited by 16 publications

(3 citation statements)

References 65 publications

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“…Early assessment of the ADME profile can reduce the risk of the last‐stage failure of an otherwise promising drug. The computational anticipation of ADMET attributes of a compound provides an insight into its practical pharmacokinetic behavior, yet experimental validation is required before its medicinal use [49] . The SwissADME server ascertains the in‐silico ADME profile of the synthesized indole‐thiadiazoles hybrids.…”

Section: Resultsmentioning

confidence: 99%

“…The computa-tional anticipation of ADMET attributes of a compound provides an insight into its practical pharmacokinetic behavior, yet experimental validation is required before its medicinal use. [49] The SwissADME server ascertains the in-silico ADME profile of the synthesized indole-thiadiazoles hybrids. Various drug-likeness parameters of indole hybrids are listed below in Table 4.…”

Section: Adme Predictionsmentioning

confidence: 99%

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Synthesis of Indole‐Linked Thiadiazoles and their Anticancer Action against Triple‐Negative Breast Cancer

Gavadia,

Rasgania,

Sahu

et al. 2024

Chemistry & Biodiversity

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With a lack of targeted therapy and significantly high metastasis, heterogeneity, and relapse rates, Triple‐Negative Breast Cancer (TNBC) offers substantial treatment challenges and demands more chemotherapeutic interventions. In the present study, indole‐endowed thiadiazole derivatives have been synthesized and screened for antiproliferative potency against the triple‐negative breast cancer MDA‐MB‐231 cell line. Compound 4h, possessing chlorophenyl moiety, displays the best anticancer potency (IC50: 0.43 μM) in the cell viability assay. The title compounds demonstrate substantial docking competency against the EGFR receptor (PDB ID: 3POZ), validating their in‐vitro ant proliferative action. With a high docking score (‐9.9 to ‐8.7 kcal/mol), the indole hybrids display significant binding propensity comparable to the co‐crystallized ligand TAK‐285 and occupy a similar strategic position in the active domain of the designated receptor. The quantum and electronic properties of the integrated templates are evaluated through DFT, and optimal values of the deduced global reactivity indices, such as energy gap, electronegativity, ionization potential, chemical potential, electrophilicity, etc., suggest their apt biochemical reactivity. The indole hybrids show near‐appropriate pharmacokinetic efficacy and bioavailability in the in‐silico studies, indicating their candidacy for potential drug usage. Promising in‐vitro anticancer action and binding interfaces project indole conjugates as potential leads in addressing the TNBC dilemma.

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Section: Resultsmentioning

confidence: 99%

Section: Adme Predictionsmentioning

confidence: 99%

Synthesis of Indole‐Linked Thiadiazoles and their Anticancer Action against Triple‐Negative Breast Cancer

Gavadia,

Rasgania,

Sahu

et al. 2024

Chemistry & Biodiversity

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“…Since then, many isoniazid derivatives have been synthesized, e.g. hydrazones (Fraza ˜o de Faria et al, 2021;Al-Khattaf et al, 2021), carboamides (Martins Gouve ˆa et al, 2022; Gavadia et al, 2023) and naphthoquinones (Reis et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, structure, ADME and biological activity of three 2,6-disubstituted thiosemicarbazone derivatives

et al. 2023

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Three new 2,6-disubstituted thiosemicarbazone derivatives of pyridine, namely, 2-{amino[6-(pyrrolidin-1-yl)pyridin-2-yl]methylidene}-N,N-dimethylhydrazine-1-carbothioamide, C13H20N6S, 2-{amino[6-(piperidin-1-yl)pyridin-2-yl]methylidene}-N,N-dimethylhydrazine-1-carbothioamide, C14H22N6S, and 2-[amino(6-phenoxypyridin-2-yl)methylidene]-N,N-dimethylhydrazine-1-carbothioamide monohydrate, C15H17N5OS·H2O, have been synthesized and characterized by NMR spectroscopy and low-temperature single-crystal X-ray diffraction. In addition, their antibacterial and anti-yeast activities have been determined. The ability of the tested compounds to inhibit bacterial growth was comparable to vancomycin as a reference drug. Compared to isoniazid (MIC 0.125 and 8 µg ml−1), the compounds showed the ability to inhibit the growth of Mycobacterium tuberculosis to a moderate degree for the standard strain and at the same level or higher (MIC 4–8 µg ml−1) for the resistant strain. All three compounds adopt the zwitterionic form in the crystal structure regardless of the presence or absence of solvent molecules.

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Design and Synthesis of Isatin‐Tagged Isoniazid Conjugates with Cogent Antituberculosis and Radical Quenching Competence: In‐vitro and In‐silico Evaluations

Gavadia,

Rasgania,

Sahu

et al. 2024

Chemistry & Biodiversity

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In pursuit of potential chemotherapeutic alternates to combat severe tuberculosis infections, novel heterocyclic templates derived from clinically approved anti‐TB drug isoniazid and isatin have been synthesized that demonstrate potent inhibitory action against Mycobacterium tuberculosis, and compound 4i with nitrophenyl motif exhibited the highest anti‐TB efficacy with a MIC value of 2.54 μM/ml. Notably, the same nitro analog 4i shows the best antioxidant efficacy among all the synthesized compounds with an IC50 value of 37.37 µg/ml, suggesting a synergistic influence of antioxidant proficiency on the anti‐TB action. The titled compounds exhibit explicit binding affinity with the InhA receptor. The befitting biochemical reactivity and near‐appropriate pharmacokinetic proficiency of the isoniazid conjugates is reflected in the density functional theory (DFT) studies and ADMET screening. The remarkable anti‐TB action of the isoniazid cognates with marked radical quenching ability may serve as a base for developing multi‐target medications to confront drug‐resistant TB pathogens. Keywords Isoniazid . Isatin . H37Rv . Antituberculosis . Antioxidant . Molecular Docking

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Synthesis of isoniazid analogs with promising antituberculosis activity and bioavailability: Biological evaluation and computational studies

Cited by 16 publications

References 65 publications

Synthesis of Indole‐Linked Thiadiazoles and their Anticancer Action against Triple‐Negative Breast Cancer

Synthesis of Indole‐Linked Thiadiazoles and their Anticancer Action against Triple‐Negative Breast Cancer

Synthesis, structure, ADME and biological activity of three 2,6-disubstituted thiosemicarbazone derivatives

Design and Synthesis of Isatin‐Tagged Isoniazid Conjugates with Cogent Antituberculosis and Radical Quenching Competence: In‐vitro and In‐silico Evaluations

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