Synthesis and biological screening of new thiadiazolopyrimidine-based polycyclic compounds

Abstract

Novel tri-and tetra-cyclic compounds based on the thiadiazolopyrimidine ring system were synthesized, and their antimicrobial activity was estimated. The obtained results evidenced the substantial efficiencies of pyrano-thiadiazolopyrimidine compounds 8a–b and 9a–b toward the two strains of gram-positive bacteria (S. aureus and B. cereus). Besides, tetracyclic pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a–b and 17a–b displayed prominent efficiencies toward the two strains of gram-negative bacteria (E. coli and P. aeruginosa). In addition, compounds 8a–b and 9a–b displayed good efficacy toward C. albicans. The activity of antiquorum sensing (anti-QS) inhibition of the newly synthesized thiadiazolopyrimidine-based compounds toward C. violaceum was tested, suggesting satisfactory activity for derivatives 16a–b, 17a–b, 8b, and 9a. The cytotoxic activity of these derivatives was screened toward various cancer cell lines (MCF-7, PC3, Hep-2, and HepG2) and standard normal fibroblast cells (WI38) by utilizing the MTT assay. The pyrazolopyrimido-thiadiazolopyrimidine derivatives 16a, 16b17a, and 17b showed potent cytotoxic efficacy against the MCF-7 cells with the IC50 values ranging from 5.69 to 9.36 µM. Also, the endorsed structural activity relationship (SAR) of the inspected thiadiazolopyrimidine derivatives provided a correlation between the chemical structure and anticancer efficiency. The in silico docking studies were implemented for silencing the hormonal signaling in the breast (PDB Code-5NQR). The results were found to be consistent with the cytotoxic activity.

Synthesis and biological studies of pyrimidine derivatives targeting metabolic enzymes

“…In the past few decades, these analogs were synthesized as PARP1 inhibitors and STAT3 inhibitors. [11,12] Also, [1,3,4]thiadiazolopyrimidine derivatives can be identified in the structure of different drugs; for example, compound I displays anthelmintic activity, [13] compound II is reported for fighting Candida albicans strain associated fungal infections, [14] and carbonic anhydrase (CA) inhibitors (compound III) and xanthine oxidase (XO) inhibitors (compound IV) are used for the treatment of glaucoma and gout, respectively [15][16][17] (Figure 2).…”