New hybrids of thiopyrimidine-five/six heterocyclic rings were synthesized and in vitro
evaluated for their antiproliferative activity against three human cancer cell lines, namely HCT116
(human colorectal carcinoma), PC-3 (human prostate adenocarcinoma) and HepG2 (human liver carcinoma)
cell lines. The most potency was elicited by the target candidates against the viability of
HCT116 cell lines. It was higher than that obtained by the positive control 5-Fluorouracil (IC50 range;
0.11-0.49 μM, IC50, 5-FU; 1.10 μM). Cell cycle analysis and apoptosis activation revealed that compound
20 induced G2/M phase arrest and apoptosis in HCT116 cells. In addition, compound 20 activates
the caspases-9 and -3, a process which might mediate the apoptosis of HCT116 cells.
structure activity relationship study was done and revealed a high predictive power R2 suggesting
goodness of the models. Furthermore, there is a good agreement between the observed pIC50 and the
predicted pIC50 values, in addition, the low RMSD and standard error values indicate the accuracy of
the model. Antimicrobial evaluation revealed that some of these compounds exhibited significant activities
against the tested pathogenic bacteria and fungi, wherein compounds 7a, 14, 15a, 21a, produced
the most potent and broad spectrum antibacterial and antifungal potency that was equivalent to
that revealed by Vibramycin and Ketoconazole (MIC; 125 μg/mL). Moreover, compounds 15a, 21c,
investigated dual potent antimicrobial and anticancer activity.