Synthesis of 2-methyl N10-substituted acridones as selective inhibitors of multidrug resistance (MDR) associated protein in cancer cells

Y C Mayur; Osman Ahmad; V V S Rajendra Prasad; M N Purohit; N Srinivasulu; S M Shanta Kumar

doi:10.2174/157340608785700180

Synthesis of 2-methyl N10-substituted acridones as selective inhibitors of multidrug resistance (MDR) associated protein in cancer cells

Med Chem. 2008 Sep;4(5):457-65. doi: 10.2174/157340608785700180.

Authors

Y C Mayur¹, Osman Ahmad, V V S Rajendra Prasad, M N Purohit, N Srinivasulu, S M Shanta Kumar

Affiliation

¹ Department of Medical Oncology, Cancer Center Amsterdam, VU Medical Center, Amsterdam, The Netherlands. mayuryc@rediffmail.com

PMID: 18782042
DOI: 10.2174/157340608785700180

Abstract

A series of N10-substituted-2-methyl acridone derivatives are synthesized and are examined for its ability to reverse P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in breast cancer cell lines MCF-7 and MCF-7/Adr. The structural requirement of in-vitro anti-cancer and reversal of drug resistance are studied. The results showed that compound 16 with four carbon spacer exhibited promising in-vitro anti-cancer and reversal of drug resistance in comparison to the other analogues.

Publication types

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

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
Acridones / chemical synthesis
Acridones / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacology*
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Cell Line, Tumor / drug effects
Cell Line, Tumor / pathology
Drug Resistance, Neoplasm*
Humans
Models, Chemical
Multidrug Resistance-Associated Proteins / antagonists & inhibitors*

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 1
Acridones
Antineoplastic Agents
Multidrug Resistance-Associated Proteins