In-silico DESIGN SCREENING OF SOME PYRAZOLONE FUSED HETEROCYCLIC ANALOGUES AS HER2 INHIBITORS TARGETING BREAST CANCER

In human breast cancers, the human epidermal development factor receptor-2 is a membrane tyrosine kinase that is overexpressed, and gene amplified. Pyrazolone fused heterocyclic moieties- thiazolidinone, carboxymethyl thiazolidinone, azetidinone are significant DNA-intercalating agents here human epidermal development factor receptor-2 amplification and over expression are linked to tumour cell proliferation and the pathway of instances in breast cancer. Few novel pyrazolone fused heterocyclic analogues are designed by in-silico-technique for their human epidermal development factor receptor-2 inhibition action. Docking patterns of compounds 4A1-4A10 are carried out against human epidermal development factor receptor-2 (PDB id-3RCD) by using Schrodinger suite 2016-2. Molecular docking study for the framed moieties 4A1-4A10 were performed by Glide XP module of Schrodinger suite. The affinity of binding as chosen based on the Glide score. Many compounds were showing good hydrophobic and hydrogen bonding communication and association in order to hinder human epidermal development factor receptor-2. The derivatives 4A1-4A10 have significant glide scores in the scope of -4.476 to - 6.234 compared with the standard Tamoxifen (-7.893). The in-silico screening properties are within the druglikeness. The results proved that this study gave a shred of evidence for the consideration of Pyrazolone fused heterocyclic analogues as potential human epidermal development factor receptor-2 inhibitors. Among the compounds, 4A1-4A10 with significant glide scores may produce significant anti-breast cancer activity and further in-vitro and in-vivo investigations may prove their therapeutic potential. The precursor phenyl hydrazine is reacted with ethylacetoacetate to give 5-methyl-2-phenyl-2,-dihydro-3H-pyrazol-one derivatives. Also, the reactivity of the precursor towards Schiff base derivatives of 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-one to give the hetero analogues of thiazolidinone derivatives was studied.