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
,
16b
17a
, and
17b
showed potent cytotoxic efficacy against the MCF-7 cells with the IC
50
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.