International Journal of Pharma and Bio Sciences
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10.22376/ijpbs.2019.10.1.p1-12
Volume 6 Issue 4
2015 (October - December)
NOVEL PHENOTHIAZINE COMPOUNDS AS THIRD GENERATION BCR-ABL TYROSINE KINASE INHIBITORS
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. Docking study was carried out and the binding affinity of the proteins with the phenothiazine compounds 3a-g and 7a-c was measured. The docking scores of the N-acylated compounds 7a-c are higher than that of the unacylated compounds. The compounds were tested for drug like molecules, used the Lipinski's rule of five. All the phenothiazine compounds (3a, 3c, 3d and 7a-c) were employed for inducing antiproliferative effect by trypan blue and MTT assay and induction of apoptosis in K562 cells. In general all the N-acylated compounds and in particular NPHC-3 with a chloro substituent in the para position of the phenyl ring appeared to be most potent molecule with an IC lessThan sub greaterThan 50 lessThan /sub greaterThan 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.
MANICKAM KARTHIGAI PRIYA, SULAIMAN ALI MUHAMMAD AND SUBBAN RAVI
Chronic myelogenous leukemia, Phenothiazine, Synthesis, characterization, Anti-proliferative activity.
707-716