2. Academic Validation
  3. Sulfonamide/sulfamate switch with a series of piperazinylureido derivatives: Synthesis, kinetic and in silico evaluation as carbonic anhydrase isoforms I, II, IV, and IX inhibitors

Sulfonamide/sulfamate switch with a series of piperazinylureido derivatives: Synthesis, kinetic and in silico evaluation as carbonic anhydrase isoforms I, II, IV, and IX inhibitors

  • Eur J Med Chem. 2020 Jan 15;186:111896. doi: 10.1016/j.ejmech.2019.111896.
Alessio Nocentini 1,  Davide Moi 2,  Alessandro Deplano 3,  Sameh M Osman 4,  Zeid A AlOthman 4,  Gianfranco Balboni 2,  Claudiu T Supuran 1,  Valentina Onnis 5
Affiliations

Affiliations

  • 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 Pharmacelera, Placa Pau Vila, 1, Sector 1, Edificio Palau de Mar, Barcelona, 08039, Spain.
  • 4 Chemistry Department, College of Science, King Saud University, P. O. Box 2455, Riyadh, 11451, Saudi Arabia.
  • 5 Department of Life and Environmental Sciences, Unit of Pharmaceutical, Pharmacological and Nutraceutical Sciences, University of Cagliari, Via Ospedale 72, I-09124, Cagliari, Italy. Electronic address: vonnis@unica.it.
PMID: 31784185 DOI: 10.1016/j.ejmech.2019.111896
Abstract

We report here a thorough structure-activity relationship (SAR) with piperazinylureido sulfamates as inhibitors of human (h) Carbonic Anhydrase (CA, EC 4.2.1.1). A SAR investigation over the structure of reported anti-cancer zinc-binder CAIs such as SLC-0111 and S4 was carried out by including the urea outer nitrogen atom into a substituted piperazine ring reducing the linker flexibility. The derivatives were assessed for the inhibition of CA I, II and IV (off-target isoforms) and the tumor-associated CA IX (Anticancer drug target). CA I and IV were not effectively inhibited, whereas many low nanomolar inhibitors were evidenced against CA II (KIs in the range of 1.0-705.5 nM), and IX (KIs in the range of 0.91-155.9 nM). Interestingly, a subset of CA II/IX selective inhibitors was detected which might represent interesting lead for the development of new Anticancer strategies.

Keywords

Antitumor; Bioisoster; Inhibitor; Metalloenzyme; Selectivity.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z