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 ... View Full Text


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Article Info

DATE

2021-03-18

AUTHORS

Suhail Razak, Tayyaba Afsar, Nousheen Bibi, Mahmoud Abulmeaty, Wajhul Qamar, Ali Almajwal, Anam Inam, Dara Al Disi, Maria Shabbir, Mashooq Ahmad Bhat

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. More... »

PAGES

6245

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    http://scigraph.springernature.com/pub.10.1038/s41598-021-84748-y

    DOI

    http://dx.doi.org/10.1038/s41598-021-84748-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1136467673

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/33737575


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