70533-96-9Relevant articles and documents
Design, synthesis and cytotoxic evaluation of a library of oxadiazole-containing hybrids
Camacho, Cristián M.,Pizzio, Marianela G.,Roces, David L.,Boggián, Dora B.,Mata, Ernesto G.,Bellizzi, Yanina,Barrionuevo, Elizabeth,Blank, Viviana C.,Roguin, Leonor P.
, p. 29741 - 29751 (2021/10/07)
The development of hybrid compounds led to the discovery of new pharmacologically active agents for some of the most critical diseases, including cancer. Herein, we describe a new series of oxadiazole-containing structures designed by a molecular hybridiz
Optimization strategy of single-digit nanomolar cross-class inhibitors of mammalian and protozoa cysteine proteases
Cianni, Lorenzo,Rocho, Fernanda dos Reis,Rosini, Fabiana,Bonatto, Vinícius,Ribeiro, Jean F.R.,Lameira, Jer?nimo,Leit?o, Andrei,Shamim, Anwar,Montanari, Carlos A.
, (2020/07/07)
Cysteine proteases (CPs) are involved in a myriad of actions that include not only protein degradation, but also play an essential biological role in infectious and systemic diseases such as cancer. CPs also act as biomarkers and can be reached by active-
Comprehensive Synthesis of Amino Acid-Derived Thiazole Peptidomimetic Analogues to Understand the Enigmatic Drug/Substrate-Binding Site of P-Glycoprotein
Patel, Bhargav A.,Abel, Biebele,Barbuti, Anna Maria,Velagapudi, Uday Kiran,Chen, Zhe-Sheng,Ambudkar, Suresh V.,Talele, Tanaji T.
, p. 834 - 864 (2018/02/17)
A novel set of 64 analogues based on our lead compound 1 was designed and synthesized with an initial objective of understanding the structural requirements of ligands binding to a highly perplexing substrate-binding site of P-glycoprotein (P-gp) and their effect on modulating the ATPase function of the efflux pump. Compound 1, a stimulator of P-gp ATPase activity, was transformed to ATPase inhibitory compounds 39, 53, and 109. The ATPase inhibition by these compounds was predominantly contributed by the presence of a cyclohexyl group in lieu of the 2-aminobenzophenone moiety of 1. The 4,4-difluorocyclohexyl analogues, 53 and 109, inhibited the photolabeling by [125I]-IAAP, with IC50 values of 0.1 and 0.76 μM, respectively. Selected compounds were shown to reverse paclitaxel resistance in HEK293 cells overexpressing P-gp and were selective toward P-gp over CYP3A4. Induced-fit docking highlighted a plausible binding pattern of inhibitory compounds in the putative-binding pocket of P-gp. The current study underscores the stringent requirement by P-gp to bind to chemically similar molecules.
