Molecular docking, pharmacokinetic studies, and in vivo pharmacological study of indole derivative 2-(5-methoxy-2-methyl-1H-indole-3-yl)-N′-[(E)-(3-nitrophenyl) methylidene] acetohydrazide as a promising chemoprotective agent against cisplatin induced organ damage

Abstract Cisplatin is an efficient anticancer drug against various types of cancers however, its usage involves side effects. We investigated the mechanisms of action of indole derivative, 2-(5-methoxy-2-methyl-1H-indol-3-yl)-N'-[(E)-(3-nitrophenyl) methylidene] acetohydrazide (MMINA) against a...

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Autores principales:	Suhail Razak, Tayyaba Afsar, Nousheen Bibi, Mahmoud Abulmeaty, Wajhul Qamar, Ali Almajwal, Anam Inam, Dara Al Disi, Maria Shabbir, Mashooq Ahmad Bhat
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8cdddadb299a44c6b6bde347ea84f9bd
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spelling	oai:doaj.org-article:8cdddadb299a44c6b6bde347ea84f9bd2021-12-02T16:31:07ZMolecular docking, pharmacokinetic studies, and in vivo pharmacological study of indole derivative 2-(5-methoxy-2-methyl-1H-indole-3-yl)-N′-[(E)-(3-nitrophenyl) methylidene] acetohydrazide as a promising chemoprotective agent against cisplatin induced organ damage10.1038/s41598-021-84748-y2045-2322https://doaj.org/article/8cdddadb299a44c6b6bde347ea84f9bd2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84748-yhttps://doaj.org/toc/2045-2322Abstract Cisplatin is an efficient anticancer drug against various types of cancers however, its usage involves side effects. We investigated the mechanisms of action of indole derivative, 2-(5-methoxy-2-methyl-1H-indol-3-yl)-N'-[(E)-(3-nitrophenyl) methylidene] acetohydrazide (MMINA) against anticancer drug (cisplatin) induced organ damage using a rodent model. MMINA treatment reversed Cisplatin-induced NO and malondialdehyde (MDA) augmentation while boosted the activity of glutathione peroxidase (GPx), and superoxide dismutase (SOD). The animals were divided into five groups (n = 7). Group1: Control (Normal) group, Group 2: DMSO group, Group 3: cisplatin group, Group 4: cisplatin + MMINA group, Group 5: MMINA group. MMINA treatment normalized plasma levels of biochemical enzymes. We observed a significant decrease in CD4+COX-2, STAT3, and TNF-α cell population in whole blood after MMINA dosage. MMINA downregulated the expression of various signal transduction pathways regulating the genes involved in inflammation i.e. NF-κB, STAT-3, IL-1, COX-2, iNOS, and TNF-α. The protein expression of these regulatory factors was also downregulated in the liver, kidney, heart, and brain. In silico docking and dynamic simulations data were in agreement with the experimental findings. The physiochemical properties of MMINA predicted it as a good drug-like molecule and its mechanism of action is predictably through inhibition of ROS and inflammation.Suhail RazakTayyaba AfsarNousheen BibiMahmoud AbulmeatyWajhul QamarAli AlmajwalAnam InamDara Al DisiMaria ShabbirMashooq Ahmad BhatNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-23 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Suhail Razak Tayyaba Afsar Nousheen Bibi Mahmoud Abulmeaty Wajhul Qamar Ali Almajwal Anam Inam Dara Al Disi Maria Shabbir Mashooq Ahmad Bhat Molecular docking, pharmacokinetic studies, and in vivo pharmacological study of indole derivative 2-(5-methoxy-2-methyl-1H-indole-3-yl)-N′-[(E)-(3-nitrophenyl) methylidene] acetohydrazide as a promising chemoprotective agent against cisplatin induced organ damage
description	Abstract Cisplatin is an efficient anticancer drug against various types of cancers however, its usage involves side effects. We investigated the mechanisms of action of indole derivative, 2-(5-methoxy-2-methyl-1H-indol-3-yl)-N'-[(E)-(3-nitrophenyl) methylidene] acetohydrazide (MMINA) against anticancer drug (cisplatin) induced organ damage using a rodent model. MMINA treatment reversed Cisplatin-induced NO and malondialdehyde (MDA) augmentation while boosted the activity of glutathione peroxidase (GPx), and superoxide dismutase (SOD). The animals were divided into five groups (n = 7). Group1: Control (Normal) group, Group 2: DMSO group, Group 3: cisplatin group, Group 4: cisplatin + MMINA group, Group 5: MMINA group. MMINA treatment normalized plasma levels of biochemical enzymes. We observed a significant decrease in CD4+COX-2, STAT3, and TNF-α cell population in whole blood after MMINA dosage. MMINA downregulated the expression of various signal transduction pathways regulating the genes involved in inflammation i.e. NF-κB, STAT-3, IL-1, COX-2, iNOS, and TNF-α. The protein expression of these regulatory factors was also downregulated in the liver, kidney, heart, and brain. In silico docking and dynamic simulations data were in agreement with the experimental findings. The physiochemical properties of MMINA predicted it as a good drug-like molecule and its mechanism of action is predictably through inhibition of ROS and inflammation.
format	article
author	Suhail Razak Tayyaba Afsar Nousheen Bibi Mahmoud Abulmeaty Wajhul Qamar Ali Almajwal Anam Inam Dara Al Disi Maria Shabbir Mashooq Ahmad Bhat
author_facet	Suhail Razak Tayyaba Afsar Nousheen Bibi Mahmoud Abulmeaty Wajhul Qamar Ali Almajwal Anam Inam Dara Al Disi Maria Shabbir Mashooq Ahmad Bhat
author_sort	Suhail Razak
title	Molecular docking, pharmacokinetic studies, and in vivo pharmacological study of indole derivative 2-(5-methoxy-2-methyl-1H-indole-3-yl)-N′-[(E)-(3-nitrophenyl) methylidene] acetohydrazide as a promising chemoprotective agent against cisplatin induced organ damage
title_short	Molecular docking, pharmacokinetic studies, and in vivo pharmacological study of indole derivative 2-(5-methoxy-2-methyl-1H-indole-3-yl)-N′-[(E)-(3-nitrophenyl) methylidene] acetohydrazide as a promising chemoprotective agent against cisplatin induced organ damage
title_full	Molecular docking, pharmacokinetic studies, and in vivo pharmacological study of indole derivative 2-(5-methoxy-2-methyl-1H-indole-3-yl)-N′-[(E)-(3-nitrophenyl) methylidene] acetohydrazide as a promising chemoprotective agent against cisplatin induced organ damage
title_fullStr	Molecular docking, pharmacokinetic studies, and in vivo pharmacological study of indole derivative 2-(5-methoxy-2-methyl-1H-indole-3-yl)-N′-[(E)-(3-nitrophenyl) methylidene] acetohydrazide as a promising chemoprotective agent against cisplatin induced organ damage
title_full_unstemmed	Molecular docking, pharmacokinetic studies, and in vivo pharmacological study of indole derivative 2-(5-methoxy-2-methyl-1H-indole-3-yl)-N′-[(E)-(3-nitrophenyl) methylidene] acetohydrazide as a promising chemoprotective agent against cisplatin induced organ damage
title_sort	molecular docking, pharmacokinetic studies, and in vivo pharmacological study of indole derivative 2-(5-methoxy-2-methyl-1h-indole-3-yl)-n′-[(e)-(3-nitrophenyl) methylidene] acetohydrazide as a promising chemoprotective agent against cisplatin induced organ damage
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8cdddadb299a44c6b6bde347ea84f9bd
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Molecular docking, pharmacokinetic studies, and in vivo pharmacological study of indole derivative 2-(5-methoxy-2-methyl-1H-indole-3-yl)-N′-[(E)-(3-nitrophenyl) methylidene] acetohydrazide as a promising chemoprotective agent against cisplatin induced organ damage

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