Design,synthesis and biological evaluation of novel ureido benzenesulfonamides incorporating 1,3,5-triazine moieties as potent carbonic anhydrase IX inhibitors |
| |
| Institution: | 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Adiyaman University, 02040 Adiyaman, Turkey;2. Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;1. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo 11566, Egypt;2. Pharmaceutical Chemistry Department, College of Pharmacy, Al-Ayen University, Ti-Qar, Iraq;3. Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, Sadat City, Menoufia, Egypt;1. State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China;2. Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China;3. Shenzhen Shuli Tech Co., Ltd, Shenzhen 518126, China;1. Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Egypt;2. Department of Oncologic Sciences, USA Mitchell Cancer Institute, 1660 Springhill Avenue, Mobile, AL 36604, USA;3. School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, Wales, UK;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Adiyaman University, 02040 Adiyaman, Turkey;2. Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche e Nutraceutiche, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;1. Department NEUROFARBA – Pharmaceutical and Nutraceutical Section, University of Firenze, via Ugo Schiff 6, I-50019 Sesto Fiorentino, Firenze, Italy;2. Department of Life and Environmental Sciences – Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, via Ospedale 72, I-09124 Cagliari, Italy;3. Department of Chemical and Pharmaceutical Sciences and LTTA, University of Ferrara, via Fossato di Mortara 17/19, I-44100 Ferrara, Italy;1. Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science & Technology Normal University, 605 Fenglin Road, Nanchang, Jiangxi 330013, China;2. College of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China |
| |
| Abstract: | A series of novel ureido benzenesulfonamides incorporating 1,3,5-triazine moieties were obtained by reacting 4-isocyanato-benzenesulfonamide (2) with 2-amino-4,6-dicholoro-1,3,5-triazine (4). The 4-(3-(4,6-dichloro-1,3,5-triazin-2-yl)ureido) benzenesulfonamide (5) was subsequently derivatized by reaction with various nucleophiles such as, morpholine, ammonia, methyl amine, dimethyl amine, and piperidine. The ureido benzenesulfonamides incorporating triazinyl moieties were investigated as inhibitors of four selected physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, namely, hCA I, II, IX, and XII which are involved in various diseases such as glaucoma, epilepsy, obesity and cancer. The membrane-bound tumor-associated isoform hCA IX was potently inhibited with these compounds with Kis in the range of 0.91–126.2 nM. Specifically, compound 7j showed great potency against hCA IX with sub-nanomolar Ki of 0.91 nM. Since hCA IX is a validated drug target for anticancer agents, these isoform-selective and potent inhibitors may be considered of interest for further medicinal/pharmacologic studies. |
| |
| Keywords: | Ureido benzenesulfonamides 1 3 5-Triazine moiety Carbonic anhydrase Isoforms Isoform-selective inhibitor Cancer |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
