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

<p>Novel 4,5-dihydropyrazole derivatives (<b>3a–i</b>), 3-(4-((3<i>aR</i>,4<i>S</i>,7<i>R</i>,7<i>aS</i>)-1,3-dioxo-3<i>a</i>,4,7,7<i>a</i>-tetrahydro-1<i>H</i>-4,7-methanoisoindol-2(3<i>H</i>)-yl)phenyl)-5-phenyl-4,5-dihydro-1<i>H</i>-pyrazole-1-carbothio amide, were obtained by the addition of thiosemicarbazide (<b>2</b>) to the chalcones (<b>1a–i</b>). The addition–cyclization of 2,4′-dibromoacetophenone (<b>4</b>) to pyrazole derivatives (<b>3a–i</b>) gave the new pyrazolyl-thiazole derivatives (<b>5a–i</b>), (3<i>aR</i>,4<i>S</i>,7<i>R</i>,7<i>aS</i>)-2-(4-(1-(4-(4-bromophenyl)thiazol-2-yl)-5-phenyl-4,5-dihydro-1<i>H</i>-pyrazol-3-yl)phenyl)-3<i>a</i>,4,7,7<i>a</i>-tetrahydro-1<i>H</i>-4,7-methanoisoindole-1,3(2<i>H</i>)-dione. Antibacterial and acetylcholinesterase (AChE) enzyme and human carbonic anhydrase (hCA) I, and II isoform inhibitory activities of the compounds <b>3a–i</b> and <b>5a–i</b> 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 <i>K</i>_i 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 <i>K</i>_i 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 <i>K</i>_i value of 70.55 ± 12.30 nM against hCA II, and 67.17 ± 9.1 nM against hCA I, and tacrine inhibited AChE showed <i>K</i>_i value of 263.67 ± 91.95.</p