Novel sulfamethoxazole and 1-(2-fluorophenyl) piperazine derivatives as potential apoptotic and antiproliferative agents by inhibition of BCL2; design, synthesis, biological evaluation, and docking studies

• Published in: 3 Biotech 2024-11, Vol.14 (11), p.269, Article 269
• Main Authors: Vadabingi, Nagalakshmamma, Mallepogu, Venkataswamy, Mallapu, Rani E., Pasala, Chiranjeevi, Poreddy, Sumithra, Bellala, Poojitha, Amineni, Umamaheswari, Cirandur, Suresh Reddy, Meriga, Balaji
• Format: Article
• Language: English
• Subjects: Agriculture; Amino acids; Antibiotics; Anticancer properties; Antiproliferatives; Antitumor activity; Antitumor agents; Apoptosis; Bcl-2 protein; Bioinformatics; Biomaterials; Biotechnology; Cancer Research; Chemistry; Chemistry and Materials Science; Cytotoxicity; Mass spectrometry; Mass spectroscopy; NMR; Nuclear magnetic resonance; Original Article; Pharmacology; Piperazine; Stem Cells; Sulfamethoxazole; Synthesis; Tumor cell lines
• ISSN: 2190-572X; 2190-5738
• DOI: 10.1007/s13205-024-04111-6

In the present study, a novel series of sulfamethoxazole and 1-(2-fluorophenyl) piperazine derivatives were designed, synthesized and characterized by FTIR, I H NMR, 13 C NMR, Mass spectrometry, CHN data, and evaluated for their efficiency as BCL2 inhibitors that could lead to potential antiproliferative activity. The ten newly synthesized compounds were screened for their therapeutic activity using MDA-MB-231 breast cancer cell lines. All the test compounds exhibited moderate to high cytotoxic activity in MTT assay. Among them, compounds 3e and 6b exhibited promising antitumor activity, as evidenced by their IC 50 values of 16.98 and 17.33 μM respectively. In addition, both compounds 3e and 6b displayed potential antioxidant and apoptosis induction properties. The qRT-PCR analysis showed down regulation of BCL2 expression and up regulation of Casp3 expression in 3e and 6b treated MDA-MB-231 cells. Further, the interaction between critical amino acids of the active domains of BCL2 and 3e and 6b was evaluated by MD simulation, and the results reflected the potent inhibitory activities of 3e and 6b . In summary, the novel compounds 3e and 6b demonstrate their potent anti-cancer properties by inducing apoptosis and selectively targeting BCL2 and caspases-3.