In Silico Study of Cembranoid-Type Diterpene Targeting Kirsten Rat Sarcoma Virus (KRAS) Gene in Lung Cancer

Teuku Baihaqi Septiady (Universitas Muhammadiyah Sumatera Utara)
Muhammad Rafli Hidayatullah (Universitas Muhammadiyah Sumatera Utara)
Ainur Rofiq (Universitas Muhammadiyah Sumatera Utara)
Afifah Endah Dwi Purianti (Universitas Muhammadiyah Sumatera Utara)
Indyra Mahrani Lubis (Universitas Muhammadiyah Sumatera Utara)
Nesya Alya Fayyaza (Universitas Muhammadiyah Sumatera Utara)
Humairah Medina Liza Lubis (Universitas Muhammadiyah Sumatera Utara)

Indonesian Journal of Pharmaceutical Science and Technology
Suppl. 4, No. 1 (2022)

Lung cancer is genetic changes in the V-Ki-ras2 gene Kirsten rat sarcoma viral oncogene homolog(KRAS), which is involved in signaling pathways related to proliferation, cell differentiation, andapoptosis. Point mutations in the KRAS gene were detected in 15% to 20% of all Non-Small Cell LungCarcinoma (NSCLCs) and about 30% of lung adenocarcinomas, with the most common mutation beingat codon 12. This study aimed to determine the binding reaction between diterpene-type cembranoidcompounds from tobacco leaves (Nicotiana tabacum L.) and KRAS in human lung cancer. We foundthe presence of a cembranoid-type diterpene active compound in the form of thunbergol (C20H34O)with Gas Chromatography and Mass Spectroscopy (GC-MS) examination. Based on the resultsof molecular docking, it was found that the diterpene-type cembranoid ligand binds to the KRASreceptor with a yield of G -7.0 kcal/mol, pKi 7.35 M, one hydrogen bond with type ILE36 (1,937 Å).In conclusion, diterpene-type cembranoid can be considered an anticancer compound because of themolecular interaction with cembranoid-type diterpene through cell proliferation and differentiationpathways, as well as apoptosis.