Exploration of selected monoterpenes as potential TRPC channel family modulator in lung cancer, an in-silico upshot

Akanksha Singh; Anamika Mishra; Abha Meena; Nidhi Mishra; Suaib Luqman

doi:10.1080/07391102.2023.2241900

Exploration of selected monoterpenes as potential TRPC channel family modulator in lung cancer, an in-silico upshot

J Biomol Struct Dyn. 2023 Aug 1:1-17. doi: 10.1080/07391102.2023.2241900. Online ahead of print.

Authors

Akanksha Singh¹, Anamika Mishra², Abha Meena^{1

3}, Nidhi Mishra², Suaib Luqman^{1

3}

Affiliations

¹ Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, Uttar Pradesh, India.
² Department of Applied Sciences, Indian Institute of Information Technology Allahabad, Prayagraj, Uttar Pradesh, India.
³ Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India.

PMID: 37526232
DOI: 10.1080/07391102.2023.2241900

Abstract

Lung cancer is still the most frequent cause of cancer-related death, accounting for nearly two million cases yearly. As cancer is a multifactorial disease, developing novel molecular therapeutics that can simultaneously target multiple associated cellular processes has become necessary. Ion channels are diverse regulators of cancer-related processes such as abnormal proliferation, invasion, migration, tumor progression, inhibition of apoptosis, and chemoresistance. Among the various families of ion channels, the transient receptor potential canonical channel family steps out in the context of lung cancer, as several members have been postulated as prognostic markers for lung cancer. Phytochemicals have been found to have health benefits in the treatment of a variety of diseases and disorders. Among phytochemicals, monoterpenes are effective in treating both the early and late stages of cancer. The molecular docking interaction analysis was conducted to evaluate the binding potential of selected monoterpenes with TRPC3, TRPC4, TRPC5, and TRPC6 involved in different phases of carcinogenesis. Amongst the selected monoterpenes, thymoquinone exhibited the highest binding energy of -6.7 kcal/mol against the TRPC4 channel, and all amino acid binding residues were similar to those of the known inhibitor for TRPC4. In addition, molecular-dynamic simulation results parameters, such as RMSD, RMSF, and Rg, indicated that thymoquinone did not impact the protein compactness and exhibited stability during the interaction. The average interaction energy between thymoquinone and TRPC4 protein was -26.85 kJ/mol. In-silico Drug-likeness and ADMET profiling indicated that thymoquinone is a druggable candidate with minimal toxicity. We propose further investigation and evaluation of thymoquinone for lead optimization and drug development.Communicated by Ramaswamy H. Sarma.

Keywords: Cancer; TRPC3; TRPC4; TRPC5; TRPC6; docking; molecular dynamics; monoterpenes; thymoquinone.

Plain language summary

Thymoquinone exhibited the highest BE −6.7 kcal/mol against the TRPC4 channel.Thymoquinone passed all drug-likeness parameters.Thymoquinone showed 99.38% of intestinal absorption in ADMET analysis.MD confirms thymoquinone forms stable molecular interaction with TRPC4.