Identification of key structural features of phosphate and thiophosphate tricyclic coumarin analogs as STS inhibitors

Steroidal sulfatase (STS) is a group of arylsulfatase C enzymes that are involved in the metabolism of steroids. The increase in the circulation of the steroidogenic hormone Estradiol (E2) is responsible for causing breast cancer. Therefore, inhibitors of STS are proved to be an attractive target in...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Srimathi Radha, K. Kathiravan Muthu
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Tricyclic coumarin analogs QSARINS Molecular docking Molecular dynamics Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/825cfee1c5534b2584b2b81403b29e15
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:825cfee1c5534b2584b2b81403b29e15
record_format	dspace
spelling	oai:doaj.org-article:825cfee1c5534b2584b2b81403b29e152021-11-20T05:13:05ZIdentification of key structural features of phosphate and thiophosphate tricyclic coumarin analogs as STS inhibitors2590-098610.1016/j.medidd.2021.100108https://doaj.org/article/825cfee1c5534b2584b2b81403b29e152021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2590098621000294https://doaj.org/toc/2590-0986Steroidal sulfatase (STS) is a group of arylsulfatase C enzymes that are involved in the metabolism of steroids. The increase in the circulation of the steroidogenic hormone Estradiol (E2) is responsible for causing breast cancer. Therefore, inhibitors of STS are proved to be an attractive target in the development of lead molecules against breast malignancy. In this work, Quantitative Structural Activity Relationship (QSAR) studies were performed on a dataset of 72 molecules of tricyclic coumarin analogs using random selection in QSARINS software and the statistical technique Genetic Algorithm coupled Multiple Linear Regression (MLR) was employed with the best model prediction R2 = 0.86 and Q2loo = 0.7913. The inclusion of descriptors Mor15m and Mor18v has developed a well-fitted and highly predictable model. Furthermore, the molecular docking and dynamics simulations helped us identify the binding interactions and estimate the stability of the complexes respectively. The binding analysis of the compounds into human sulfatase protein (PDB code: 1P49) resulted in prominent hydrophobic interactions with Arg98, Val486, Phe488, Gly100, Val101, and Lys368. The top-scoring compound 9o and compound 41 were studied for stability analysis in comparison with the standard Irosustat and the RMSD was found to be 5.4 Å. Based on our findings, we report the inclusion of the necessary structural features of coumarin derivatives leads to the development of potent candidates for further development.Srimathi RadhaK. Kathiravan MuthuElsevierarticleTricyclic coumarin analogsQSARINSMolecular dockingMolecular dynamicsPharmacy and materia medicaRS1-441ENMedicine in Drug Discovery, Vol 12, Iss , Pp 100108- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Tricyclic coumarin analogs QSARINS Molecular docking Molecular dynamics Pharmacy and materia medica RS1-441
spellingShingle	Tricyclic coumarin analogs QSARINS Molecular docking Molecular dynamics Pharmacy and materia medica RS1-441 Srimathi Radha K. Kathiravan Muthu Identification of key structural features of phosphate and thiophosphate tricyclic coumarin analogs as STS inhibitors
description	Steroidal sulfatase (STS) is a group of arylsulfatase C enzymes that are involved in the metabolism of steroids. The increase in the circulation of the steroidogenic hormone Estradiol (E2) is responsible for causing breast cancer. Therefore, inhibitors of STS are proved to be an attractive target in the development of lead molecules against breast malignancy. In this work, Quantitative Structural Activity Relationship (QSAR) studies were performed on a dataset of 72 molecules of tricyclic coumarin analogs using random selection in QSARINS software and the statistical technique Genetic Algorithm coupled Multiple Linear Regression (MLR) was employed with the best model prediction R2 = 0.86 and Q2loo = 0.7913. The inclusion of descriptors Mor15m and Mor18v has developed a well-fitted and highly predictable model. Furthermore, the molecular docking and dynamics simulations helped us identify the binding interactions and estimate the stability of the complexes respectively. The binding analysis of the compounds into human sulfatase protein (PDB code: 1P49) resulted in prominent hydrophobic interactions with Arg98, Val486, Phe488, Gly100, Val101, and Lys368. The top-scoring compound 9o and compound 41 were studied for stability analysis in comparison with the standard Irosustat and the RMSD was found to be 5.4 Å. Based on our findings, we report the inclusion of the necessary structural features of coumarin derivatives leads to the development of potent candidates for further development.
format	article
author	Srimathi Radha K. Kathiravan Muthu
author_facet	Srimathi Radha K. Kathiravan Muthu
author_sort	Srimathi Radha
title	Identification of key structural features of phosphate and thiophosphate tricyclic coumarin analogs as STS inhibitors
title_short	Identification of key structural features of phosphate and thiophosphate tricyclic coumarin analogs as STS inhibitors
title_full	Identification of key structural features of phosphate and thiophosphate tricyclic coumarin analogs as STS inhibitors
title_fullStr	Identification of key structural features of phosphate and thiophosphate tricyclic coumarin analogs as STS inhibitors
title_full_unstemmed	Identification of key structural features of phosphate and thiophosphate tricyclic coumarin analogs as STS inhibitors
title_sort	identification of key structural features of phosphate and thiophosphate tricyclic coumarin analogs as sts inhibitors
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/825cfee1c5534b2584b2b81403b29e15
work_keys_str_mv	AT srimathiradha identificationofkeystructuralfeaturesofphosphateandthiophosphatetricycliccoumarinanalogsasstsinhibitors AT kkathiravanmuthu identificationofkeystructuralfeaturesofphosphateandthiophosphatetricycliccoumarinanalogsasstsinhibitors
_version_	1718419551449776128

Identification of key structural features of phosphate and thiophosphate tricyclic coumarin analogs as STS inhibitors

Ejemplares similares