Molecules (Nov 2023)

Therapeutic Study of Cinnamic Acid Derivative for Oxidative Stress Ablation: The Computational and Experimental Answers

  • Oluwafemi Adeleke Ojo,
  • Akingbolabo Daniel Ogunlakin,
  • Rotdelmwa Filibis Maimako,
  • Gideon Ampoma Gyebi,
  • Christopher Busayo Olowosoke,
  • Odunayo Anthonia Taiwo,
  • Tobiloba Christiana Elebiyo,
  • David Adeniyi,
  • Bolaji David,
  • Matthew Iyobhebhe,
  • Juliana Bunmi Adetunji,
  • Damilare IyinKristi Ayokunle,
  • Adebola Busola Ojo,
  • Ramzi A. Mothana,
  • Abdullah R. Alanzi

DOI
https://doi.org/10.3390/molecules28217425
Journal volume & issue
Vol. 28, no. 21
p. 7425

Abstract

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This study aimed to examine the therapeutic activity of the cinnamic acid derivative KAD-7 (N′-(2,4-dichlorobenzylidene)-3-(4-methoxyphenyl) acrylohydrazide) on Fe2+-induced oxidative hepatic injury via experimental and computational models. In addition, the role of ATPase and ectonucleoside triphosphate diphosphohydrolase (ENTPDase) in the coordination of cellular signals is speculated upon to proffer suitable therapeutics for metabolic stress disorder upon their inhibition. While we know little about therapeutics with flexible dual inhibitors for these protein targets, this study was designed to screen KAD-7’s (N′-(2,4-dichlorobenzylidene)-3-(4-methoxyphenyl) acrylohydrazide) inhibitory potential for both protein targets. We induced oxidative hepatic damage via the incubation of hepatic tissue supernatant with 0.1 mM FeSO4 for 30 min at 37 °C. We achieved the treatment by incubating the hepatic tissues with KAD-7 under the same conditions. The catalase (CAT), glutathione (GSH), malondialdehyde (MDA), ATPase, and ENTPDase activity were all measured in the tissues. We predicted how the drug candidate would work against ATPase and ENTPDase targets using molecular methods. When hepatic injury was induced, there was a significant decrease in the levels of the GSH, CAT, and ENTPDase (p p 4 by reducing oxidative stress and purinergic actions. Our studies indicate that KAD-7 could be developed as a therapeutic option since it can flexibly inhibit both ATPase and ENTPDase.

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