2. Academic Validation
  3. Carvacrol-conjugated 3-Hydroxybenzoic Acids: Design, Synthesis, cardioprotective potential against doxorubicin-induced Cardiotoxicity, and ADMET study

Carvacrol-conjugated 3-Hydroxybenzoic Acids: Design, Synthesis, cardioprotective potential against doxorubicin-induced Cardiotoxicity, and ADMET study

  • Bioorg Med Chem Lett. 2024 Nov 15:113:129973. doi: 10.1016/j.bmcl.2024.129973.
Rini Retnosari 1,  Kentaro Oh-Hashi 2,  Azizah Ugusman 3,  Satirah Zainalabidin 4,  Jalifah Latip 5,  Natsuhisa Oka 6
Affiliations

Affiliations

  • 1 Department of Chemical Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia; International Joint Department of Materials Science and Engineering Between National University of Malaysia and Gifu University, Graduate School of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Department of Chemistry, Universitas Negeri Malang, Jl. Semarang No. 5 Malang, Indonesia.
  • 2 Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501- 1193, Japan; Center for One Medicine Innovative Translational Research (COMIT), Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
  • 3 Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; Cardiovascular and Pulmonary (CardioResp) Research Group, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia.
  • 4 Programme of Biomedical Science, Centre for Toxicology and Health Risk Studies (CORE), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, 50300 Kuala Lumpur, Malaysia; Cardiovascular and Pulmonary (CardioResp) Research Group, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia.
  • 5 Department of Chemical Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia; Smart Material and Sustainable Product Innovation (SMatSPIn) Research, Universiti Kebangsaan Malaysia, UKM Bangi 43600, Selangor, Malaysia. Electronic address: jalifah@ukm.edu.my.
  • 6 International Joint Department of Materials Science and Engineering Between National University of Malaysia and Gifu University, Graduate School of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Center for One Medicine Innovative Translational Research (COMIT), Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan; Institute for Glyco-core Research (iGCORE), Gifu University, Gifu 501-1193, Japan. Electronic address: oka.natsuhisa.f9@f.gifu-u.ac.jp.
PMID: 39317301 DOI: 10.1016/j.bmcl.2024.129973
Abstract

Carvacrol (CA) is a phenolic monoterpene renowned for its diverse pharmacological benefits, particularly its cardioprotective effects. Concurrently, phenolic acids have also demonstrated promise in mitigating drug-induced cardiotoxicity. Focusing on combating doxorubicin-induced cardiotoxicity (DIC), the research aims to synthesize novel cardioprotective agents by combining CA with 3-hydroxybenzoic acid (3HA). Doxorubicin, an Anticancer drug, poses cardiovascular risks as its adverse effect, prompting the exploration of hybrid compounds. Various linker molecules, including alkyl and acyl with different carbon lengths, were investigated to understand their impact on bioactivity. In vitro testing on the DOX-induced H9c2 cell death model revealed the effectiveness of a CA conjugate in preserving cardiomyocyte viability. In silico analysis highlighted favorable drug-like properties and low toxicity of the conjugate. This study sheds light on molecular hybridization's potential in developing cardioprotective agents, emphasizing CA's pivotal role in combating DIC.

Keywords

Carvacrol; Doxorubicin-induced cardiotoxicity; Drug-likeness; H9c2 cells; Hydroxybenzoic acid; Molecular hybridization.

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