Aug 2026· Asian Journal of Chemistry· Vol 38, pp. 2102-2108· 0 citations· 19 references
TL;DR
The findings suggest that the lead molecule induces apoptosis in cancer cells by inhibiting the interaction between BCL-XL and BAD, a mechanism supported by in silico studies.
Abstract
Present work describes the development and evaluation of novel piperazine–pyrrolidone acyl hydrazide hybrids as potential anticancer agents for breast cancer treatment. The cytotoxic activities of these compounds were determined against human breast cancer cell lines (MCF-7) by alamar blue assay. A compound 1-(4-(4-chloro-2-fluorophenyl)piperazin-1-yl)-5-oxopyrrolidine-3-carbohydrazide (7b) showed the highest cytotoxicity with IC50 value of 1.46 µM. The lead candidate exhibited superior activity compared to the standard drug tamoxifen (1.75 µM) and was approximately two-fold less potent than doxorubicin (0.73 µM). A structure–activity relationship (SAR) analysis was carried out to understand the effect of structural modifications on anticancer activity. The findings suggest that the lead molecule induces apoptosis in cancer cells by inhibiting the interaction between BCL-XL and BAD, a mechanism supported by in silico studies.
The results revealed that the synthesised derivative 3h has potential binding affinity hence blocking the activity, and the synthesised piperazine derivatives are identified as promising lead compounds for further anticancer optimization.
Vaibhav Daund, Pooja Agarwal, A. Jain et al.· Asian Journal of Chemistry· 0 citations
Among the synthesized compounds, PBc1 exhibited the greatest in vitro antiproliferative activity against both MDA-MB-231 and SK-OV-3 cell lines, suggesting that PBc1 is a promising compound for further biological and mechanistic investigation.
Prachita Gauns Dessai, Parixit J. Bhandurge, C. Nazareth et al.· Journal of the Iranian Chemi...· 0 citations
This study reports an efficient synthesis of 6-(4-methoxyphenyl)-3-aryl-[1,2,4]triazolo[4,3-b]pyridazine derivatives via oxidative cyclization of the corresponding hydrazones using iodobenzene diacetate as a mild and metal-free oxidizing agent. The structures of the synthesized compounds were confirmed by 1H NMR, 13C NMR, FTIR, and mass spectrometry. Their in vitro anticancer activity was evaluated against the MCF-7 breast cancer cell line, where four compounds (7a, 7c, 7d, and 7f) exhibited notable cytotoxic effects. Molecular docking studies suggested favorable binding interactions of these compounds with several cancer-related targets, including human 17β-hydroxysteroid dehydrogenase, topoisomerase IIα, p73 tetramerization domain, Bcl2-xL, EGFR tyrosine kinase, and survivin. Docking of the complete compound series (7a-7j) further supported the observed activity trends. These findings indicate that triazolopyridazine derivatives represent promising scaffolds for further investigation as anticancer agents. IBD was used as an environment friendly reagent for the synthesis of 1,2,4-triazolo[4,3-b]pyridazines by oxidative cyclization of hydrazone derivatives. 1,2,4-Triazoles showed excellent anticancer activity against breast cancer Michigan Cancer Foundation-7 (MCF-7) cells. The molecular docking studies were carried out with several enzymes associated with breast cancer to find the effective binding of the synthesized compounds.
S. Malik, R. Soni, M. Sihag et al.· Discover Chemistry· 0 citations
It is demonstrated that benzofuran-furan-pyrano[2,3-c]pyrazole hybrids possess promising multifaceted in vitro anticancer activity by inhibiting cancer cell proliferation, migration, invasion, and clonogenicity while inducing ROS-mediated mitochondrial apoptosis, highlighting these hybrid scaffolds as attractive candidates for further anticancer drug development.
E. Hutanu, Bassam A. Najri, A. Abdelsalam et al.· RSC Advances· 0 citations
The limited efficacy and resistance associated with current anticancer therapies necessitate the development of novel agent, particularly for aggressive malignancies. In this study, a series of fluorine-substituted isoindolinone-amino acid conjugates was designed and evaluated for antiproliferative activity using a phenotypic screening approach. A library of 24 compounds was screened against lung, breast and skin cancer cell lines, among which 11 derivatives demonstrated promising antiproliferative activity with IC50 values ranging from 7.36 to 41.99 µM. SAR analysis revealed that incorporation of trifluoromethoxy (-OCF3) substitution with Trp, Tyr, and Phe conjugation significantly enhances activity relative to trifluoromethyl (-CF3) and mono-fluoro analogues. The lead compounds 9c, 9d, 9e, and 10c markedly inhibited cancer cell proliferation, clonogenic survival, and migration, while inducing apoptosis and a pronounced S-phase cell-cycle arrest. Network pharmacology identified CDK2 and GSK3B as key hub genes associated with cell-cycle regulation. Mechanistic studies demonstrated downregulation of CDK2 and PCNA, activation of p53-p21 signaling pathway, and increased γ-H2AX expression, indicating replicating-associated damage. Molecular docking predicted favorable interactions with the CDK2 catalytic pocket, which was further validated by an in vitro CDK2/CyclinA2 kinase inhibition and reduced CDK2 protein expression determined by western blot analysis, collectively implicating CDK2 as a key molecular target. Furthermore, compounds 9c, 9d, 9e and 10c exhibited significant tumor growth inhibition (TGI) values of 53.50%, 79.47%, 64.50% and 69.14% respectively, in the 4T1 murine breast cancer model without evident systemic toxicity. Collectively, these findings identify fluorinated isoindolinone-amino acid conjugates as promising anticancer leads targeting CDK2-associated cell-cycle signaling against triple-negative breast cancer.
Soma Mandal, Rajat Choudhary, A.A.I. Parvaj Laskar et al.· Biomedicine & pharmacotherap...· 0 citations
Background: Glioblastoma (GBM) is the most aggressive subtype of malignant glioma. Current therapeutic options remain limited, highlighting the need for the development of novel compounds capable of improving the efficacy of standard treatments. This study aimed to evaluate the biological activity of a series of pyrazolone-based hydrazone compounds (TPPs) in vitro GBM cell lines. Methods: The eight TPPs were synthesized by a nucleophilic addition reaction of different substituted hydrazines with 1-(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-2-phenylethan-1-one and tested on two human GBM cell lines, T98 and U87. The cytotoxic effects were evaluated via MTT assay. The most active compound was further investigated at IC50 and IC25 concentrations to evaluate mechanisms of cellular damage, including reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨm) changes. Additional assays included colony formation, cell cycle analysis, and evaluation of DNA damage and apoptosis markers. Results: TPP25 exhibited the highest activity with IC50 values of 11.01 μM (95% CI: 10.42 to 11.64) and 13.12 μM (95% CI: 10.23 to 16.87) on T98 and U87 lines, respectively. Treatment induced early ROS production and mitochondrial depolarization, along with a significant reduction in colony formation. Cell cycle analysis revealed accumulation in the sub-G0 phase, consistent with increased cell death, supported by propidium iodide uptake. Furthermore, the results suggest the involvement of an apoptotic-like mechanism as supported by Annexin V positivity, γ-H2AX upregulation and transient caspase-3 activation. Conclusions: TPP25 demonstrates significant in vitro cytotoxicity, likely driven by a pro-apoptotic mechanism. This profile positions it as a potential lead compound for further preclinical evaluation, supporting its future transition into in vivo GBM models.
G. Cameli, Alessia Piergentili, Eleonora Spinozzi et al.· Pharmaceuticals· 0 citations
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