Zero Hunger (SDG 2), Good Health & Well-being (SDG 3)
Optimising Cannabidiol for cancer therapy: a DFT, molecular docking, and cytotoxicity study in cutaneous squamous cell carcinoma Krishna K Govender 1* , Andrea J Josiah 1,2 , Penny P Govender 1 , Werner Cordier 3 , Margo Nell 3 , Suprakas Sinha Ray 1,2 1 Department of Chemical Sciences, University of Johannesburg, 2028, Johannesburg, South Africa, 2Centre for Nanostructured and Advanced Materials, DSI-CSIR Nanotechnology Innovation Centre, Council for Scientific and Industrial Research, Pretoria 0001, South Africa, 2 Department of Pharmacology, University of Pretoria, Pretoria 0002, South Africa E-mail: krishnag@uj.ac.za Cancer represents a significant global healthcare challenge owing to its diverse nature, necessitating continuous innovation in treatment strategies. [1] This study evaluates the therapeutic potential of cannabidiol (CBD) in comparison with 5-fluorouracil (5-FU) against cutaneous squamous cell carcinoma (cSCC) through quantum chemistry, molecular docking, and cytotoxicity assays. The optimised geometry of CBD was calculated using Density Functional Theory (DFT) employing the M06-2X functional and 6-31+G(d,p) basis set, revealed a small HOMO-LUMO gap indicative of high reactivity. Experimental FTIR spectra closely matched DFT-calculated vibrational frequencies, particularly the O-H stretch (experimental: 3519 cm – ¹; theoretical: 3581 cm – ¹), validating the computational methodology. The DFT simulations were conducted with Gaussian 16 revision C01 [2] and were visualised via GaussView 6.1. [3] Molecular docking was performed using the Glide [4] docking program in Schrodinger Maestro [5] , which revealed that CBD exhibited a higher binding affinity towards the CB1 receptor (-9.986 kcal/mol) compared to 5-FU (-3.760 kcal/mol). Molecular dynamics simulations together with binding free energy calculations (MM-GBSA) also confirmed CBD’s enhanced affinity (-69.696 kcal/mol) over 5-FU (-28.241 kcal/mol). Cytotoxicity assays in A431 cells further confirmed CBD’s efficacy, with an IC50 of 2.76 ± 1.08 μM , surpassing 5-FU 5.61 ± 1.07 μM. Key words: Cannabidiol, DFT, Docking, Squamous cell carcinoma, SRB assay References 1. The global challenge of cancer. Nat Cancer 1 , 2020 , pp. 1-2. 2. Gaussian 16, Revision B.01 M. J. Frisch et al , Gaussian, Inc., Wallingford CT, 2016 . 3. Dennington, R., Keith, T.A. and Millam, J.M, GaussView 6.0.16. Semichem Inc., Shawnee Mission, 2016 .
4. Schrödinger Release 2024-3 : Glide, Schrödinger, LLC, New York, NY, 2024 . 5. Schrödinger Release 2024-3 : Maestro, Schrödinger, LLC, New York, NY, 2024 .
P10
© The Author(s), 2025
Made with FlippingBook Learn more on our blog