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
- PMID: 39421851
- PMCID: PMC11480306
- DOI: 10.1007/s13205-024-04111-6
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
Abstract
In the present study, a novel series of sulfamethoxazole and 1-(2-fluorophenyl) piperazine derivatives were designed, synthesized and characterized by FTIR, IH NMR,13C 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 IC50 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.
Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04111-6.
Keywords: Anti-cancer; Antioxidant activity; Apoptosis; BCL2; Piperazine; Sulfamethoxazole.
© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
Conflict of interest statement
Conflict of interestThere are no competing financial interests declaredby the authors.
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References
-
- Abdelrheem DA, Abd El-Mageed HR, Mohamed HS, Rahman AA, Elsayed KNM, Ahmed SA (2021) Bis-indole alkaloid caulerpin from a new source Sargassumplatycarpum: isolation, characterization, in vitro anticancer activity, binding with nucleobases by DFT calculations and MD simulation. J BiomolStructDyn 39(14):5137–5147. 10.1080/07391102.2020.1784285 - PubMed
-
- Alessandria L, Schilirò T, Degan R, Traversi D, Gilli G (2014) Cytotoxic response in human lung epithelial cells and ion characteristics of urban-air particles from Torino, a northern Italian city. Environ Sci Pollut Res Int 21(8):5554–5564. 10.1007/s11356-013-2468-1 - PubMed
-
- Ananda Kumar CS, Benaka Prasad SB, Vinaya K, Chandrappa S, Thimmegowda NR, Kumar YC, Swarup S, Rangappa KS (2009) Synthesis and in vitro antiproliferative activity of novel 1-benzhydrylpiperazine derivatives against human cancer cell lines. Eur J Med Chem 44(3):1223–1229. 10.1016/j.ejmech.2008.09.025 - PubMed
-
- Arockiaraj J, Palanisamy R, Arasu A, Sathyamoorthi A, Kumaresan V, Bhatt P, Chaurasia MK, Pasupuleti M, Gnanam AJ (2015) An anti-apoptotic B-cell lymphoma-2 (BCL-2) from Channastriatus: Sequence analysis and delayed and advanced gene expression in response to fungal, bacterial and poly I: C induction. Mol Immunol 63(2):586–594. 10.1016/j.molimm.2014.07.018 - PubMed
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