SYNTHESIS OF NOVEL CYCLOHEXANONE DERIVATIVES AS BCR-ABL T1351 INHIBITORS

  • Sulaiman Ali Muhammad Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore 641021 Tamilnadu, India
  • Subash Suganya Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore 641021 Tamilnadu, India
  • Subban Ravi Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore 641021 Tamilnadu, India
  • Senniappan Venkatachalapathi Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore 641021 Tamilnadu, India

Abstract

Objective: Several 3(rd) generation inhibitors are being developed for the treatment of patients with Chronic myelogenous leukemia (CML). The present work mainly aims to discover novel small molecular inhibitors against important molecular target T3151 ABL mutant involved in leukemia.

Methods: Docking study was carried out and the binding affinity of the proteins with the phenothiazine compounds 3a-h and 7a-c was measured. The docking scores of the N-acylated compounds 7a-c are higher than 3a-h. The drug likeliness of these compounds was tested by the Lipinski’s rule of five. The phenothiazine compounds with good docking scores and 7a-c were synthesized and screened by in-vitro methods for inducing antiproliferative effect by trypan blue and MTT assay and induction of apoptosis in K562 cells.

Results: All the N-acylated compounds and, in particular, 7c with a chloro substituent in the para position of the phenyl ring appeared to be most potent molecule with an IC50 value of 32.44 and 24.01(µg/ml) by trypan blue and MTT assay respectively. Further, a dose-dependent increase in LDH release was observed, confirming the antiproliferative potential of the compounds.

Conclusion: The compounds 7a-c was tested for antiproliferative effect against K562 cell lines by MTT assay LDH assay and Trypan blue assay. All the compounds 7a-h behaves as 3(rd) generation inhibitors for the treatment of patients with Chronic myelogenous leukemia (CML). These can act as a template for the further development and optimization studies.

 

Keywords: Synthesis, Phenothiazine, Cyclohexanone derivatives, Chronic myelogenous leukemia, Molecular docking, Anti-proliferative activity

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Author Biography

Sulaiman Ali Muhammad, Department of Chemistry, Karpagam Academy of Higher Education, Coimbatore 641021 Tamilnadu, India

Research Scholar, Department of Chemistry

Karpagam Academy of Higher education, Coimbatore-21

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How to Cite
Muhammad, S. A., S. Suganya, S. Ravi, and S. Venkatachalapathi. “SYNTHESIS OF NOVEL CYCLOHEXANONE DERIVATIVES AS BCR-ABL T1351 INHIBITORS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 7, no. 12, Oct. 2015, pp. 195-9, https://innovareacademics.in/journals/index.php/ijpps/article/view/8995.
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