Design and discovery of novel monastrol-1,3,5-triazines as potent anti-breast cancer agent via attenuating Epidermal Growth Factor Receptor tyrosine kinase

Abstract A novel series of hybrid analogues of monastrol-1,3,5-triazine were designed and developed via one-pot synthesis using Bi(NO3)3 as a catalyst. Entire compounds were evaluated for their anticancer activity against HeLa (cervical cancer), MCF-7 (breast cancer), HL-60 (Human promyelocytic leuk...

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Autores principales:	Jitendra Kumar Srivastava, Girinath G. Pillai, Hans Raj Bhat, Amita Verma, Udaya Pratap Singh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a3f39bb0c73b423ba93335c416a0a7bc
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spelling	oai:doaj.org-article:a3f39bb0c73b423ba93335c416a0a7bc2021-12-02T16:06:10ZDesign and discovery of novel monastrol-1,3,5-triazines as potent anti-breast cancer agent via attenuating Epidermal Growth Factor Receptor tyrosine kinase10.1038/s41598-017-05934-52045-2322https://doaj.org/article/a3f39bb0c73b423ba93335c416a0a7bc2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05934-5https://doaj.org/toc/2045-2322Abstract A novel series of hybrid analogues of monastrol-1,3,5-triazine were designed and developed via one-pot synthesis using Bi(NO3)3 as a catalyst. Entire compounds were evaluated for their anticancer activity against HeLa (cervical cancer), MCF-7 (breast cancer), HL-60 (Human promyelocytic leukemia), HepG2 (Hepatocellular carcinoma) and MCF 12A (normal epithelial breast cell line) using MTT assay, where they showed highest inhibitory activity against MCF-7. The molecules were also found to be non-toxic to MCF 12A cells. These molecules showed considerable inhibitory percentage against Epidermal Growth Factor Receptor tyrosine kinase (EGFR-TK), in in-vitro assay. Molecular docking study was carried out on the analogs and reference compound (Erlotinib) into the ATP binding site of EGFR-TK domain (PDB ID:1M17) to elucidate vital structural residues necessary for bioactivity. The effect of most active compound 7l was also estimated in-vivo in DMBA induced mammary tumor in female Sprague-Dawley rats. The effect of anti-breast cancer effect of 7l was quantified on the basis of tumour incidence, body weight and tumor volume in DMBA-induced rats. Its effect on biochemical parameters, such as antioxidant status (SOD, CAT, GPX and GSH) and lipid peroxidation was also studied. The compound 7l showed inhibition of EGFR downstream signalling in the western blot analysis.Jitendra Kumar SrivastavaGirinath G. PillaiHans Raj BhatAmita VermaUdaya Pratap SinghNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-18 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jitendra Kumar Srivastava Girinath G. Pillai Hans Raj Bhat Amita Verma Udaya Pratap Singh Design and discovery of novel monastrol-1,3,5-triazines as potent anti-breast cancer agent via attenuating Epidermal Growth Factor Receptor tyrosine kinase
description	Abstract A novel series of hybrid analogues of monastrol-1,3,5-triazine were designed and developed via one-pot synthesis using Bi(NO3)3 as a catalyst. Entire compounds were evaluated for their anticancer activity against HeLa (cervical cancer), MCF-7 (breast cancer), HL-60 (Human promyelocytic leukemia), HepG2 (Hepatocellular carcinoma) and MCF 12A (normal epithelial breast cell line) using MTT assay, where they showed highest inhibitory activity against MCF-7. The molecules were also found to be non-toxic to MCF 12A cells. These molecules showed considerable inhibitory percentage against Epidermal Growth Factor Receptor tyrosine kinase (EGFR-TK), in in-vitro assay. Molecular docking study was carried out on the analogs and reference compound (Erlotinib) into the ATP binding site of EGFR-TK domain (PDB ID:1M17) to elucidate vital structural residues necessary for bioactivity. The effect of most active compound 7l was also estimated in-vivo in DMBA induced mammary tumor in female Sprague-Dawley rats. The effect of anti-breast cancer effect of 7l was quantified on the basis of tumour incidence, body weight and tumor volume in DMBA-induced rats. Its effect on biochemical parameters, such as antioxidant status (SOD, CAT, GPX and GSH) and lipid peroxidation was also studied. The compound 7l showed inhibition of EGFR downstream signalling in the western blot analysis.
format	article
author	Jitendra Kumar Srivastava Girinath G. Pillai Hans Raj Bhat Amita Verma Udaya Pratap Singh
author_facet	Jitendra Kumar Srivastava Girinath G. Pillai Hans Raj Bhat Amita Verma Udaya Pratap Singh
author_sort	Jitendra Kumar Srivastava
title	Design and discovery of novel monastrol-1,3,5-triazines as potent anti-breast cancer agent via attenuating Epidermal Growth Factor Receptor tyrosine kinase
title_short	Design and discovery of novel monastrol-1,3,5-triazines as potent anti-breast cancer agent via attenuating Epidermal Growth Factor Receptor tyrosine kinase
title_full	Design and discovery of novel monastrol-1,3,5-triazines as potent anti-breast cancer agent via attenuating Epidermal Growth Factor Receptor tyrosine kinase
title_fullStr	Design and discovery of novel monastrol-1,3,5-triazines as potent anti-breast cancer agent via attenuating Epidermal Growth Factor Receptor tyrosine kinase
title_full_unstemmed	Design and discovery of novel monastrol-1,3,5-triazines as potent anti-breast cancer agent via attenuating Epidermal Growth Factor Receptor tyrosine kinase
title_sort	design and discovery of novel monastrol-1,3,5-triazines as potent anti-breast cancer agent via attenuating epidermal growth factor receptor tyrosine kinase
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a3f39bb0c73b423ba93335c416a0a7bc
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Design and discovery of novel monastrol-1,3,5-triazines as potent anti-breast cancer agent via attenuating Epidermal Growth Factor Receptor tyrosine kinase

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