Synthesis and evaluation of 5-Aryl-3-(4-hydroxyphenyl)-1,3,4-oxadiazole-2-(3H)-thiones as P-glycoprotein inhibitors

Chatchanok Loetchutinat; François Chau; Samlee Mankhetkorn

doi:10.1248/cpb.51.728

Synthesis and evaluation of 5-Aryl-3-(4-hydroxyphenyl)-1,3,4-oxadiazole-2-(3H)-thiones as P-glycoprotein inhibitors

Chem Pharm Bull (Tokyo). 2003 Jun;51(6):728-30. doi: 10.1248/cpb.51.728.

Authors

Chatchanok Loetchutinat¹, François Chau, Samlee Mankhetkorn

Affiliation

¹ Laboratory of Physical Chemistry Molecular and Cellular Biology, Faculty of Science, Burapha University, Thailand.

PMID: 12808255
DOI: 10.1248/cpb.51.728

Abstract

5-Aryl-3-(4-hydroxyphenyl)-1,3,4-oxadiazole-2(3H)-thiones 3 were prepared by cyclocondensation of 1-(4-hydroxyphenyl)-2-aroylhydrazines with thiophosgene. All compounds exhibited antiproliferation activity in K562, IC(50) ranging from 24 to 94 micro M comparable efficacy with apigenin and genistein and showed more potent antiproliferation of K562/adr cells, highly expressing P-glycoprotein. Compounds 3g, 3e and 3a inhibited the function of P-glycoprotein with the alpha(0.5) equal to 10+/-3 micro M, 21+/-5 micro M and 34+/-7 micro M, respectively.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology
Cell Survival / drug effects
Humans
Inhibitory Concentration 50
K562 Cells
Magnetic Resonance Spectroscopy
Molecular Structure
Oxazoles / chemical synthesis*
Oxazoles / chemistry
Oxazoles / pharmacology
Thiones / chemical synthesis*
Thiones / chemistry
Thiones / pharmacology

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 1
Antineoplastic Agents
Oxazoles
Thiones