Inhibition of MMP2-PEX by a novel ester of dihydroxy cinnamic and linoleic acid from the seagrass Cymodocea serrulata

Abstract Matrix metalloproteinases (MMPs) are pivotal for cancer cell migration and metastasis which are generally over-expressed in such cell types. Many drugs targeting MMPs do so by binding to the conserved catalytic domains and thus exhibit poor selectivity due to domain-similarities with other...

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Autores principales:	V. S. Christina, R. Lakshmi Sundaram, V. Sivamurugan, D. Thirumal Kumar, C. D. Mohanapriya, V. L. Shailaja, S. P. Thyagarajan, C. George Priya Doss, K. Mary Elizabeth Gnanambal
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dbcf18e089ee464eabd1034aab9e7cd4
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spelling	oai:doaj.org-article:dbcf18e089ee464eabd1034aab9e7cd42021-12-02T15:56:56ZInhibition of MMP2-PEX by a novel ester of dihydroxy cinnamic and linoleic acid from the seagrass Cymodocea serrulata10.1038/s41598-021-90845-92045-2322https://doaj.org/article/dbcf18e089ee464eabd1034aab9e7cd42021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90845-9https://doaj.org/toc/2045-2322Abstract Matrix metalloproteinases (MMPs) are pivotal for cancer cell migration and metastasis which are generally over-expressed in such cell types. Many drugs targeting MMPs do so by binding to the conserved catalytic domains and thus exhibit poor selectivity due to domain-similarities with other proteases. We report herein the binding of a novel compound [3-(E-3,4-dihydroxycinnamaoyloxyl)-2-hydroxypropyl 9Z, 12Z-octadeca-9, 12-dienoate; Mol. wt: 516.67 Da], (C 1 ), isolated from a seagrass, Cymodocea serrulata to the unconserved hemopexin-like (PEX) domain of MMP2 (− 9.258 kcal/mol). MD simulations for 25 ns, suggest stable ligand-target binding. In addition, C 1 killed an ovarian cancer cell line, PA1 at IC50: 5.8 μM (lesser than Doxorubicin: 8.6 µM) and formed micronuclei, apoptotic bodies and nucleoplasmic bridges whilst causing DNA laddering, S and G2/M phase dual arrests and MMP disturbance, suggesting intrinsic apoptosis. The molecule increased mRNA transcripts of BAX and BAD and down-regulated cell survival genes, Bcl-xL, Bcl-2, MMP2 and MMP9. The chemical and structural details of C 1 were deduced through FT-IR, GC–MS, ESI–MS, 1H and 13C NMR [both 1D and 2D] spectra.V. S. ChristinaR. Lakshmi SundaramV. SivamuruganD. Thirumal KumarC. D. MohanapriyaV. L. ShailajaS. P. ThyagarajanC. George Priya DossK. Mary Elizabeth GnanambalNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q V. S. Christina R. Lakshmi Sundaram V. Sivamurugan D. Thirumal Kumar C. D. Mohanapriya V. L. Shailaja S. P. Thyagarajan C. George Priya Doss K. Mary Elizabeth Gnanambal Inhibition of MMP2-PEX by a novel ester of dihydroxy cinnamic and linoleic acid from the seagrass Cymodocea serrulata
description	Abstract Matrix metalloproteinases (MMPs) are pivotal for cancer cell migration and metastasis which are generally over-expressed in such cell types. Many drugs targeting MMPs do so by binding to the conserved catalytic domains and thus exhibit poor selectivity due to domain-similarities with other proteases. We report herein the binding of a novel compound [3-(E-3,4-dihydroxycinnamaoyloxyl)-2-hydroxypropyl 9Z, 12Z-octadeca-9, 12-dienoate; Mol. wt: 516.67 Da], (C 1 ), isolated from a seagrass, Cymodocea serrulata to the unconserved hemopexin-like (PEX) domain of MMP2 (− 9.258 kcal/mol). MD simulations for 25 ns, suggest stable ligand-target binding. In addition, C 1 killed an ovarian cancer cell line, PA1 at IC50: 5.8 μM (lesser than Doxorubicin: 8.6 µM) and formed micronuclei, apoptotic bodies and nucleoplasmic bridges whilst causing DNA laddering, S and G2/M phase dual arrests and MMP disturbance, suggesting intrinsic apoptosis. The molecule increased mRNA transcripts of BAX and BAD and down-regulated cell survival genes, Bcl-xL, Bcl-2, MMP2 and MMP9. The chemical and structural details of C 1 were deduced through FT-IR, GC–MS, ESI–MS, 1H and 13C NMR [both 1D and 2D] spectra.
format	article
author	V. S. Christina R. Lakshmi Sundaram V. Sivamurugan D. Thirumal Kumar C. D. Mohanapriya V. L. Shailaja S. P. Thyagarajan C. George Priya Doss K. Mary Elizabeth Gnanambal
author_facet	V. S. Christina R. Lakshmi Sundaram V. Sivamurugan D. Thirumal Kumar C. D. Mohanapriya V. L. Shailaja S. P. Thyagarajan C. George Priya Doss K. Mary Elizabeth Gnanambal
author_sort	V. S. Christina
title	Inhibition of MMP2-PEX by a novel ester of dihydroxy cinnamic and linoleic acid from the seagrass Cymodocea serrulata
title_short	Inhibition of MMP2-PEX by a novel ester of dihydroxy cinnamic and linoleic acid from the seagrass Cymodocea serrulata
title_full	Inhibition of MMP2-PEX by a novel ester of dihydroxy cinnamic and linoleic acid from the seagrass Cymodocea serrulata
title_fullStr	Inhibition of MMP2-PEX by a novel ester of dihydroxy cinnamic and linoleic acid from the seagrass Cymodocea serrulata
title_full_unstemmed	Inhibition of MMP2-PEX by a novel ester of dihydroxy cinnamic and linoleic acid from the seagrass Cymodocea serrulata
title_sort	inhibition of mmp2-pex by a novel ester of dihydroxy cinnamic and linoleic acid from the seagrass cymodocea serrulata
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/dbcf18e089ee464eabd1034aab9e7cd4
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Inhibition of MMP2-PEX by a novel ester of dihydroxy cinnamic and linoleic acid from the seagrass Cymodocea serrulata

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