Effectiveness of sesquiterpene derivatives from Cinnamomum genus in nicotine replacement therapy through blocking acetylcholine nicotinate: a computational analysis

Abstract

Cigarette smoking poses various health risks, such as increasing the susceptibility to respiratory infections, contributing to osteoporosis, causing reproductive issues, delaying postoperative recovery, promoting ulcer formation and heightening the risk of diabetes. While many harmful effects of smoking are attributed to other cigarette components, it is nicotine’s pharmacological effects that underlie tobacco addiction. Nicotine replacement therapy (NRT) aims to alleviate the urge to smoke and mitigate physiological and psychomotor withdrawal symptoms by delivering nicotine. This study explores the potential of sesquiterpene derivative compounds derived from the Cinnamomum genus using computational techniques. The research incorporates molecular docking analyses, Lipinski’s rule of five filtration for drug-likeness, pharmacokinetic and toxicity predictions to assess safety profiles and molecular dynamics (MD) simulations to gauge interaction stability. The findings reveal that all sesquiterpene derivative compounds from the Cinnamomum genus can potentially inhibit nicotinic acetylcholine receptors (nAChRs), particularly nAChRÿ7. However, only abscisic acid exhibit active inhibition, along with suitable drug properties, pharmacokinetics and toxicity profiles. MD studies confirm the stability of interactions between abscisic acid with nAChRÿ7. Consequently, abscisic acid, as sesquiterpene derivatives from the Cinnamomum genus, holds substantial promise for further investigation as nAChRÿ7 inhibitors.

Communicated by Ramaswamy H. Sarma

Keywords:

• Cinnamomum genus
• nicotine replacement therapy (NRT)
• nicotinic acetylcholine receptors (nAChRs)
• inhibitor nAChRÿ7
• computational study

Disclosure statement

The authors declare no conflict of interest.

Author contributions

Conceptualization, A.D.R., S.A.D., T.M.F., and C.C.L; methodology, A.D.R., and T.M.F.; software, T.M.F.; validation, T.M.F.; formal analysis, T.M.F.; investigation, A.D.R., and T.M.F.; resources, A.D.R., and S.A.D.; data curation, A.D.R.; writing—original-draft preparation, A.D.R., and T.M.F.; writing—review and editing, A.D.R., S.A.D., T.M.F., and C.C.L; visualization, T.M.F.; supervision, A.D.R., S.A.D., T.M.F., and C.C.L; All authors have read and agreed to the published version of the manuscript.

Additional information

Funding

The author extends gratitude to the Ministry of Education, Culture, Research, and Technology (Kemdikbudristek) of the Republic of Indonesia for the invaluable support received through the 2023 Penelitian Dosen Pemula grant program, under No. 180/E5/PG.02.00.PL/2023.