|
|||||
|
|
Synthesis of new 3-(2-mercapto-4-oxo-4H-quinazolin-3-yl)-benzenesulfonamides with strong inhibition properties against the tumor associated carbonic anhydrases IX and XII |
|
| Authors: | Murat Bozdag Ahmed Mahmoud Alafeefy Abdul Malik Altamimi Fabrizio Carta Claudiu T Supuran Daniela Vullo |
| Institution: | 1. Università degli Studi di Firenze, Dipartimento Neurofarba, Sezione di Scienze Farmaceutiche, Polo Scientifico, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy;2. Chemistry Department, Kulliyyah of Science, International Islamic University, Kuantan, Malaysia;3. Pharmaceutical Chemistry Dept., College of Pharmacy, Prince Sattam Bin Abdulaziz University, Saudi Arabia;4. Università degli Studi di Firenze, Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy |
| Abstract: | We report a series of novel metanilamide-based derivatives 3a–q bearing the 2-mercapto-4-oxo-4H-quinazolin-3-yl moiety as tail. All compounds were synthesized by means of straightforward condensation procedures and were investigated in vitro for their inhibition potency against the human (h) carbonic anhydrase (CA; EC 4.2.1.1.1) isoforms I, II, IX and XII. Among all compounds tested the 6-iodo 3g and the 7-fluoro 3i derivatives were the most potent inhibitors against the tumor associated CA IX and XII isoform (KIs 1.5 and 2.7 nM respectively for the hCA IX and KIs 0.57 and 1.9 nM respectively for the hCA XII).The kinetic data reported here strongly support compounds of this type for their future development as radiotracers in tumor pathologies which are strictly dependent on the enzymatic activity of the hCA IX and XII isoforms. |
| Keywords: | Carbonic anhydrase inhibitors (CAIs) Quinazolines Tumors Imaging |
| 本文献已被 ScienceDirect 等数据库收录！ | |