Exploration of the cytotoxic and microtubule disruption potential of novel imidazo[1,5-a]pyridine-based chalcones.

IF 4.1 4区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY RSC medicinal chemistry Pub Date : 2025-01-08 DOI:10.1039/d4md00838c

Ramu Gopathi, Mommuleti Pradeep Kumar, Gangasani Jagadeesh Kumar, Syamprasad N P, Bheeshma Geetanjali Kodiripaka, V G M Naidu, Bathini Nagendra Babu

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Abstract

In continuation of our efforts to develop new anticancer compounds, a new series of imidazo[1,5-a]pyridine-chalcone derivatives was designed, synthesized, characterized, and evaluated for its cytotoxicity against five human cancer cell lines, i.e., breast (MDA-MB-231), colon (RKO), bone (Mg-63), prostate (PC-3), and liver (HepG2) cell lines, as well as a normal cell line (HEK). Among the synthesized compounds, two exhibited promising cytotoxicity against the MDA-MB-231 cell line with IC₅₀ values of 4.23 ± 0.25 μM and 3.26 ± 0.56 μM. We also studied apoptotic induction of the compounds using annexin V-FITC/PI staining, and ROS-mediated mitochondrial damage was elucidated using DCFDA, followed by JC-1 staining. The potential activity of the compounds was further confirmed by immuno-fluorescence and molecular docking studies, which revealed the anticancer activity of active compounds through binding and microtubule disruption.

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新型咪唑[1,5-a]吡啶查尔酮的细胞毒性和微管破坏潜力的探索。

为了继续开发新的抗癌化合物，我们设计、合成、表征了一系列新的咪唑[1,5-a]吡啶查尔酮衍生物，并评估了其对五种人类癌细胞系的细胞毒性，即乳腺癌（MDA-MB-231）、结肠癌（RKO）、骨（Mg-63）、前列腺（PC-3）、肝脏（HepG2）细胞系以及正常细胞系（HEK）。其中2个化合物对MDA-MB-231细胞株具有良好的细胞毒性，IC50值分别为4.23±0.25 μM和3.26±0.56 μM。我们还通过annexin V-FITC/PI染色研究了化合物对细胞凋亡的诱导作用，并通过DCFDA和JC-1染色研究了ros介导的线粒体损伤。通过免疫荧光和分子对接研究进一步证实了化合物的潜在活性，揭示了活性化合物通过结合和微管破坏的抗癌活性。

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