Synthesis of α,β-Unsaturated Carbonyl-Based Compounds, Oxime and Oxime Ether Analogs as Potential Anticancer Agents for Overcoming Cancer Multidrug Resistance by Modulation of Efflux Pumps in Tumor Cells

Hua Li Qin, Jing Leng, Cheng Pan Zhang, Ibrahim Jantan, Muhammad Wahab Amjad, Muhammad Sher, Muhammad Naeem-Ul-Hassan, Muhammad Ajaz Hussain, Bukhari Syed Nasir Abbas

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Sixty-nine novel α,β-unsaturated carbonyl based compounds, including cyclohexanone, tetralone, oxime, and oxime ether analogs, were synthesized. The antiproliferative activity determined by using seven different human cancer cell lines provided a structure-activity relationship. Compound 8ag exhibited high antiproliferative activity against Panc-1, PaCa-2, A-549, and PC-3 cell lines, with IC50 value of 0.02 μM, comparable to the positive control Erlotinib. The ten most active antiproliferative compounds were assessed for mechanistic effects on BRAFV600E, EGFR TK kinases, and tubulin polymerization, and were investigated in vitro to reverse efflux-mediated resistance developed by cancer cells. Compound 8af exhibited the most potent BRAFV600E inhibitory activity with an IC50 value of 0.9 μM. Oxime analog 7o displayed the most potent EGFR TK inhibitory activity with an IC50 of 0.07 μM, which was analogous to the positive control. Some analogs including 7f, 8af, and 8ag showed a dual role as anticancer and MDR reversal agents.

Original languageEnglish
Pages (from-to)3549-3561
Number of pages13
JournalJournal of Medicinal Chemistry
Volume59
Issue number7
DOIs
Publication statusPublished - 28 Apr 2016

Fingerprint

Oximes
Multiple Drug Resistance
Antineoplastic Agents
Ether
Inhibitory Concentration 50
Tetralones
Cell Line
Neoplasms
Structure-Activity Relationship
Tubulin
Polymerization
Phosphotransferases

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Synthesis of α,β-Unsaturated Carbonyl-Based Compounds, Oxime and Oxime Ether Analogs as Potential Anticancer Agents for Overcoming Cancer Multidrug Resistance by Modulation of Efflux Pumps in Tumor Cells. / Qin, Hua Li; Leng, Jing; Zhang, Cheng Pan; Jantan, Ibrahim; Amjad, Muhammad Wahab; Sher, Muhammad; Naeem-Ul-Hassan, Muhammad; Hussain, Muhammad Ajaz; Syed Nasir Abbas, Bukhari.

In: Journal of Medicinal Chemistry, Vol. 59, No. 7, 28.04.2016, p. 3549-3561.

Research output: Contribution to journalArticle

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