Synthesis and biological screening of new thiadiazolopyrimidine-based polycyclic compounds

• Published in: Scientific reports Vol. 11; no. 1; p. 15750
• Main Author: Alqahtani, Alaa M
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 03.08.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antimicrobial activity; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Bacteria; Bacteria - drug effects; Breast; Cell Proliferation; Cytotoxicity; E coli; Fungi - drug effects; Gram-negative bacteria; Gram-positive bacteria; High-Throughput Screening Assays; Humans; Neoplasms - drug therapy; Neoplasms - pathology; Polycyclic compounds; Polycyclic Compounds - chemical synthesis; Polycyclic Compounds - pharmacology; Pyrimidines - chemistry; Strains (organisms); Thiadiazoles - chemistry; Tumor cell lines; Tumor Cells, Cultured
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-95241-x

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 IC 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.