Synthesis and biological evaluation of novel 3-(quinolin-4-ylamino)benzenesulfonamides as carbonic anhydrase isoforms I and II inhibitors

Journal of Enzyme Inhibition and Medicinal Chemistry

Sora Paik¹  So Ha Lee¹  Ahmed Elkamhawy²  Eun Joo Roh³  Silvia Bua⁴  Claudiu T. Supuran⁴  Mohammad M. Al-Sanea⁵  Mohamed A. Abdelgawad⁶  Wagdy M. Eldehna⁷ 

[1] Chemical Kinomics Research Center, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea;Chemical Kinomics Research Center, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea;Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt;Chemical Kinomics Research Center, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea;Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul, Republic of Korea;Department of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Firenze, Italy;Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia;Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka, Saudi Arabia;Department of Pharmaceutical Organic Chemistry, Beni-Suef University, Beni-Suef, Egypt;Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egyp;

关键词: carbonic anhydrase;    quinolines;    synthesis;    cytosolic isoforms hCA I and II;   

DOI  :  10.1080/14756366.2019.1652282

来源: publisher

【 摘 要 】

Carbonic anhydrases (CAs, EC 4.2.1.1) are crucial metalloenzymes that are involved in diverse bioprocesses. We report the synthesis and biological evaluation of novel series of benzenesulfonamides incorporating un/substituted ethyl quinoline-3-carboxylate moieties. The newly synthesised compounds were in vitro evaluated as inhibitors of the cytosolic human (h) isoforms hCA I and II. Both isoforms hCA I and II were inhibited by the quinolines reported here in variable degrees: hCA I was inhibited with KIs in the range of 0.966–9.091 μM, whereas hCA II in the range of 0.083–3.594 μM. The primary 7-chloro-6-flouro substituted sulphfonamide derivative 6e (KI = 0.083 μM) proved to be the most active quinoline in inhibiting hCA II, whereas, its secondary sulfonamide analog failed to inhibit the hCA II up to 10 μM, confirming the crucial role of the primary sulphfonamide group, as a zinc-binding group for CA inhibitory activity.

【 授权许可】

CC BY