Design and synthesis of triazole-functionalized isatin hybrids with potent anti-proliferative action against triple-negative breast cancer MDA-MB-231 cell line: a hybrid pharmacophore approach

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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.

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

Gavadia,

Rasgania,

Sahu

et al. 2024

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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

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

Design, Synthesis, Anti‐Proliferative, and Apoptotic Assessment of Spirocyclopropyl Oxindole–Isatin Hybrids on Triple‐Negative Breast Cancer

Preeti,

Raza,

Sharma

et al. 2024

A series of 1H‐1,2,3‐triazole‐tethered spirocyclopropyl oxindole‐isatin hybrids were synthesized using a copper‐promoted click reaction and evaluated for their anti‐proliferative activities against triple‐negative breast cancer cell lines. The most potent compound in the series outperformed tamoxifen and 5‐fluorouracil, with selectivity indices (SI) of 1.60 and 1.99 against MDA‐MB‐468 and MDA‐MB‐231 cancer cells, respectively. The Caspase 3/7 7‐AAD assay showed live cell populations of 72.10% and 49.20% after 24 and 48 hours, respectively, indicating that the cytotoxic effect is mediated through the caspase apoptotic pathway. Molecular docking studies further suggested the compound's potential as an EGFR inhibitor, highlighting its promise as a therapeutic agent.