HomeCannabis MedicineQSAR Modelling of Biological Activity in Cannabinoids with Quantum Similarity Combinations of Charge Fitting Schemes and 3D-QSAR

QSAR Modelling of Biological Activity in Cannabinoids with Quantum Similarity Combinations of Charge Fitting Schemes and 3D-QSAR

April 20, 2023

Chem Biodivers. 2023 Apr 7:e202201086. doi: 10.1002/cbdv.202201086. Online ahead of print.

ABSTRACT

Quantitative structure-activity relationship(QSAR) modeled the biological activities of 30 cannabinoids with quantum similarity descriptors(QSD) and Comparative Molecular Field Analysis(CoMFA). The PubChem[https://pubchem.ncbi.nlm.nih.gov/] database provided the geometries, binding affinities(Ki) to the cannabinoid receptors type 1(CB1) and 2(CB2), and the median lethal dose(LD50) to breast cancer cells. An innovative quantum similarity approach combining (self)-similarity indexes calculated with different charge-fitting schemes under the Topo-Geometrical Superposition Algorithm(TGSA) were used to obtain QSARs. The determination coefficient(R2) and leave-one-out cross-validation[Q2(LOO)] quantified the quality of multiple linear regression and support vector machine models. This approach was efficient in predicting the activities, giving predictive and robust models for each endpoint [pLD50: R2=0.9666 and Q2(LOO)=0.9312; pKi(CB1): R2=1.0000 and Q2(LOO)=0.9727, and pKi(CB2): R2=0.9996 and Q2(LOO)=0.9460], where p is the negative logarithm. The descriptors based on the electrostatic potential encrypted better electronic information involved in the interaction. Moreover, the similarity-based descriptors generated unbiased models independent of an alignment procedure. The obtained models showed better performance than those reported in the literature. An additional 3D-QSAR CoMFA analysis was applied to 15 cannabinoids, taking THC as a template in a ligand-based approach. From this analysis, the region surrounding the amino group of the SR141716 ligand is the more favorable for the antitumor activity.

PMID:37029452 | DOI:10.1002/cbdv.202201086

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About The Author

Patrick Blanchard MD

Meet Dr. Blanchard Dr. Blanchard’s medical practice is an embodiment of Integrative health which brings conventional and complementary approaches together in a coordinated way. Conveniently located in sunny Florida and over the internet with ValiseMD’s secure HIPPA compliant telXmed servers. Since 1994, patients with a wide range of challenging medical problems have achieved optimum health using the best of natural medicine, judiciously combined with high-tech innovations. Breakthroughs are often achieved even after patients have consulted mainstream specialists and holistic practitioners. Dr. Blanchard is founder and CEO of ValiseMD, Inc. He is board certified in Family Medicine since 1994 and awarded Fellow of the American Academy of Family Physicians in 2001. He received the ‘Teacher of the Year’ award from the University of Kansas School of Medicine at completion of his residency in Family Medicine. He completed a fellowship at Wake Forest University in the field of vascular neurosonology. He holds a medical patent in the field of Gastroenterology. He holds an unrestricted license to practice medicine and surgery in Florida. He started his medical career as a Emergency Medical Technician, then as a Paramedic and later a Medical Doctor.