Synthesis and Investigation of Carbonic Anhydrase I and II Activity of Dihydrobenzo[h]Quinazolin-2-yl Thiourea Compounds

Abstract

Thirteen novel compounds in a series of dihydrobenzo[h]quinazolin-2-yl thiourea compounds (7a-m) were synthesized and characterized using FT-IR, H-1, C-13 NMR spectroscopy, and elemental analysis. Some inhibition parameters including IC50 and inhibition constant values (K-i) were determined for all the compounds. All studied compounds exhibited potent inhibition against carbonic anhydrases (CAs). They inhibited CAs with the IC50 values of 30.45 to 94.00 mu M (K-i: 28.27-61.01 mu M) for hCA I and 21.80 to 78.00 mu M (K-i: 17.84-57.96 mu M) for hCA II. The most active compounds were found to be compound 7m for hCA I (K-i: 28.27 mu M) and compound 7d for hCA II (K-i : 17.84 mu M). The absorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) study revealed that all the derivatives had good oral bioavailability with respect to Lipinski's rule of five and Jorgensen's rule of three. All derivatives in the series can be considered as outstanding multitarget inhibitors for further investigations.