Development of Promising Thiopyrimidine-Based Anti-cancer and Antimicrobial Agents: Synthesis and QSAR Analysis

Title:Development of Promising Thiopyrimidine-Based Anti-cancer and Antimicrobial Agents: Synthesis and QSAR Analysis

Volume: 19 Issue: 15

Author(s): Yasmin M. Syam, Manal M. Anwar*, Eman R. Kotb, Samia A. Elseginy, Hanem M. Awad and Ghada E.A. Awad

Affiliation:

• Department of Therapeutic Chemistry, National Research Centre, Dokki, Cairo 12622,Egypt

Keywords: Thiopyrimidine, synthesis, anticancer, apoptosis, caspases-9, -3, QSAR.

Abstract: Objective & Methodology: 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).

Results: 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. Quantitative structure activity relationship study was done and revealed a high predictive power R2 suggesting goodness of the models.

Conclusion: 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.

Cite this article as:

Syam M. Yasmin, Anwar M. Manal *, Kotb R. Eman , Elseginy A. Samia , Awad M. Hanem and Awad E.A. Ghada , Development of Promising Thiopyrimidine-Based Anti-cancer and Antimicrobial Agents: Synthesis and QSAR Analysis, Mini-Reviews in Medicinal Chemistry 2019; 19 (15) . https://dx.doi.org/10.2174/1389557518666180330110828

DOI https://dx.doi.org/10.2174/1389557518666180330110828	Print ISSN 1389-5575
Publisher Name Bentham Science Publisher	Online ISSN 1875-5607