Synthesis and investigation of antibacterial activities and carbonic anhydrase and acetyl cholinesterase inhibition profiles of novel 4,5-dihydropyrazol and pyrazolyl-thiazole derivatives containing methanoisoindol-1,3-dion unit

Abstract

ABSTRACTNovel 4,5-dihydropyrazole derivatives (3a–i), 3-(4-((3aR,4S,7R,7aS)-1,3-dioxo-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindol-2(3H)-yl)phenyl)-5-phenyl-4,5-dihydro-1H-pyrazole-1-carbothio amide, were obtained by the addition of thiosemicarbazide (2) to the chalcones (1a–i). The addition–cyclization of 2,4′-dibromoacetophenone (4) to pyrazole derivatives (3a–i) gave the new pyrazolyl-thiazole derivatives (5a–i), (3aR,4S,7R,7aS)-2-(4-(1-(4-(4-bromophenyl)thiazol-2-yl)-5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)phenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione. Antibacterial and acetylcholinesterase (AChE) enzyme and human carbonic anhydrase (hCA) I, and II isoform inhibitory activities of the compounds 3a–i and 5a–i were investigated. Some of the compounds showed promising antibacterial activity. In addition, the hCA II and I were effectively inhibited by the lately synthesized derivatives, with Ki values in the range of 18.90 ± 2.37 −58.25 ± 13.62 nM for hCA II and 5.72 ± 0.98 −37.67 ± 5.54 nM for hCA I. Also, the Ki parameters of these compounds for AChE were obtained in the range of 25.47 ± 11.11 − 255.74 ± 82.20 nM. Also, acetazolamide, clinical molecule, was used as a CA standard inhibitor that showed Ki value of 70.55 ± 12.30 nM against hCA II, and 67.17 ± 9.1 nM against hCA I, and tacrine inhibited AChE showed Ki value of 263.67 ± 91.95.