Unveiling Betulinic Acid as a Potent CDK4 Inhibitor for Cancer Therapeutics

Indian Journal of Pharmaceutical Education and Research

  • Basiouny El-Gamal1Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, SAUDI ARABIA.
  • Thoraya A-Elgadir1Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, SAUDI ARABIA.
  • Ayyub Ali Patel1Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, SAUDI ARABIA.
  • Mohamed Abd Ellatif1Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, SAUDI ARABIA., 2Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura, EGYPT.
  • Khalid Ali Nasif1Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, SAUDI ARABIA., 3Department of Medical Biochemistry, Faculty of Medicine, Minia University, Minia, EGYPT.
  • Awad Saeed Alsamghan4Department of Family and Community Medicine, King Khalid University, Abha, SAUDI ARABIA.
  • Arshi Malik5CQRL BITS LLP, Chennai, Tamil Nadu, INDIA.
  • Mohamed Babiker Abd Elrouf1Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, SAUDI ARABIA.
  • Imad Alghawanmeh1Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, SAUDI ARABIA.
  • Marwa Saeed1Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, SAUDI ARABIA.
  • Osama Haroun Ahmed6Department of Clinical Biochemistry, Shifajizan Polyclinics Laboratory, Jazan, SAUDI ARABIA.
  • Soha Makki7Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha, SAUDI ARABIA.
  • Haitham Elshaikh8Planaletix, Dubai, UNITED ARAB EMIRATES.
  • Yasser Ali8Planaletix, Dubai, UNITED ARAB EMIRATES.

Volume 58 Issue 4 Pages 1117-1129

DOI: 10.5530/ijper.58.4.123

Abstract

Background: CDK4 play a pivotal role in cell cycle regulation, making it a critical players in the development and progression of cancer. In recent years, there has been a growing interest in targeting CDK4 for cancer therapeutics, with a focus on the identification and development of small molecule inhibitors. Materials and Methods: This work, using a strong in silico and in vitro methodology, reveals Betulinic Acid's inhibitory efficacy against CDK4 for cancer therapy. Betulinic Acid, a pentacyclic triterpenoid with a variety of characteristics, has emerged as a promising CDK4 inhibitor. Results: The study identifies key CDK4 binding sites using high-resolution structural modeling and cavity detection. Betulinic Acid's highest fitness and predicted binding affinity were found, supporting its drug-likeness properties. Its pharmacokinetic viability, biological properties, and cytotoxicity assays show its concentration-dependent effects on cancer cells (A549 and NCI-H460). Molecular-level validations reveal a significant decrease in CDK4 mRNA expression and kinase activity, reinforcing its potential as a CDK4 inhibitor. Conclusion: In conclusion, this comprehensive study bridges structural insights with experimental validations, positioning Betulinic Acid as a promising therapeutic agent for CDK4 inhibition in cancer, particularly lung cancer. The findings contribute significantly to drug discovery, paving the way for further preclinical and clinical investigations in the quest for effective cancer treatments.

Keywords

  • Betulinic Acid
  • Cancer therapeutics
  • CDK4 inhibition
  • Lung cancer treatment
  • Molecular docking
  • Pharmacokinetic viability
IJOPP

Loading…