New thiobarbituric acid scaffold-based small molecules: Synthesis, cytotoxicity, 2D-QSAR, pharmacophore modelling and in-silico ADME screening.

A series of twenty five new thiobarbituric acid derivatives, viz. 3a-h, 4-7, 8a-c, 9, 10a-c, 11 and 12a-d, were designed and synthesized as potential cytotoxic agents. In-vitro screening of the new compounds against the three human cancer cell lines Caco-2, HepG-2 and MCF-7 was performed to assess their intrinsic activity. Compound 12d exhibited potent sub-micromolar activity against HepG-2 and MCF-7 (IC50 = 0.07 and 0.08 µM, respectively). In-silico pharmacophore modelling of this chemotype compounds disclosed a five features' pharmacophore model representing essential steric and electronic fingerprints essential for activity. Finally, a 2D-QSAR model was devised to quantitatively correlate the 2D molecular feature descriptors of this series of thiobarbiturates with their cytotoxic activity against MCF-7. Finally, in silico evaluation of the physicochemical and ADME properties of these derivatives was performed.

Synthesis of new pyrrolo[2,3-d]pyrimidine derivatives as antibacterial and antifungal agents.

A series of new pyrrole derivatives, pyrrolo[2,3-d]pyrimidine derivatives, pyrrolotriazolopyrimidines and pyrrolotetrazolopyrimidines were synthesized. The evaluation of their antimicrobial activities against Staphylococcus aureus, Escherichia coli, and Candida albicans were carried out. Pyrrolo[2,3-d]pyrimidines 3a-d, 7a,e, 11d exhibited excellent activity against C. albicans with MIC 0.31-0.62 mg/mL. These compounds displayed better antifungal activity than that of standard drug (fluconazole with MIC 1.5 mg/mL). Furthermore, pyrrolo[2,3-d]pyrimidines 3b,c, 7e exhibited the best activity against S. aureus with MIC 0.31 mg/mL, compared with the standard drug (ampicillin with MIC 0.62 mg/mL). The rest of the compounds were found to be inactive against bacteria and fungi.