Exploration of phthalazine bearing oxadiazolyl–triazole hybrids as selective breast cancer agents: computational docking interactions

Abstract

In this study, a series of novel phthalazine derivatives bearing 1,3,4–oxadiazolyl–1,2,3–triazole moiety were designed, synthesized, and evaluated for anticancer activity. The formation targeted compounds were confirmed for their structure by means of various spectral–analytical techniques like ¹H-NMR, ¹³C-NMR, FT-IR, elemental analysis, and mass spectrum. All synthesized compounds were screened for anticancer activity against three different human breast cancer cell lines MCF-7, T-47D, and MDA-MB-231. From screening results, compound 5f exhibited the most potent anticancer activity (IC₅₀ = 10.21 ± 2.2, 7.53 ± 0.1 µM) towards T-47D, MCF-7 cell lines and 4b, 5b demonstrated the highest % growth of inhibition (61.25 ± 0.52, 62.48 ± 0.20 µg/mL) against T-47D, and MCF-7 cell lines, respectively, which is equivalent to that reported by the standard cisplatin. The docking study strongly favours compound 4d, 5a, 5e, and 5f to be a dehydrogenase type 1 complexed in breast cancer inhibitor as it displayed a similar interaction to cisplatin (3HB4). Ligand 5f exhibited amino acid interactions and having docking score –11.53 kcal/mol, respectively. The in-silico pharmacokinetics studies support the results obtained from docking and biological evaluation and displayed favourable pharmacokinetic profile for a drug to be orally available.

Bull. Chem. Soc. Ethiop. 2025, 39(4), 731-748.                                                               

DOI: https://dx.doi.org/10.4314/bcse.v39i4.10