Synthesis, Hemolytic Studies, and In Silico Modeling of Novel Acefylline–1,2,4-Triazole Hybrids as Potential Anti-cancer Agents against MCF-7 and A549

[Image: see text] A series of novel theophylline-7-acetic acid (acefylline)-derived 1,2,4-triazole hybrids with N-phenyl acetamide moieties (11a–j) have been synthesized and tested for their inhibitory (in vitro) potential against two cancer cell lines, A549 (lung) and MCF-7 (breast), using MTT assay. Among these derivatives, 11a, 11c, 11d, 11g, and 11h displayed remarkable activity against both cancer cell lines having cell viability values in the 21.74 ± 1.60–55.37 ± 4.60% range compared to acefylline (86.32 ± 1.75%) using 100 μg/μL concentration of compounds. These compounds were further screened against the A549 cancer cell line (lung) to find their half-maximal inhibitory concentration (IC(50)) by applying various concentrations of these compounds. Compound 11g (2-(5-((1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)methyl)-4-phenyl-4H-1,2,4-triazol-3-ylthio)-N-p-tolylacetamide) with the least IC(50) value (1.25 ± 1.36 μM) was discerned as a strong inhibitor of cancer cell multiplication in both cell lines (A549 and MCF-7). Their hemolytic studies revealed that all of them had very low cytotoxicity. Finally, in silico modeling was carried out to find the mode of binding of the highly active compound (11g), which was according to the results of anti-cancer activity.