Molecular docking and prediction of ADME/drug-likeness properties of potentially active antidiabetic compounds isolated from aqueous-methanol extracts of Gymnema sylvestre and Combretum micranthum

Abstract

Gymnema sylvestre and Combretum micranthum are well known for their ethno-medicinal uses in the northwest of Nigeria. In our recent study, we demonstrated the antidiabetic and antioxidant activities of the aqueous-methanol extracts of the two plants and identified some potentially active compounds. The present study aimed to conduct molecular docking and ADME/drug-likeness screening of the identified potentially active candidate compounds from aqueous-methanol extracts of G. sylvestre and C. micranthum leaves by using in silico techniques. Molecular docking of compounds on target proteins (α-amylase, α-glucosidase, and phosphorylated insulin receptor tyrosine kinase) was performed using Molsoft ICM-pro 3.8-3. The physicochemical, ADME, and drug-likeness parameters were computed using the SwissADME online program. The result corroborated the antidiabetic activities of the plants with significant binding interactions between compounds A (2,2-dimethyl-3-[4-(acetyloxy)phenyl]-4-ethy-l2H-1-benzopyran-7-ol acetate), D (9,13-di-cis-retinoic acid), E (4-hydroxycinnamic acid), F ((-)-11-hydroxy-9,10-dihydrojasmonic acid), G (colnelenic acid), H (glyinflanin A), I (6,8a-seco-6,8a-deoxy-5-oxoavermectin “2a” aglycone), and J (3-deshydroxysappanol trimethyl ether) and at least one of the three target proteins. Four compounds, namely A (2,2-dimethyl-3-[4-(acetyloxy)phenyl]-4-ethyl-2H-1-benzopyran-7-ol acetate), E (4-hydroxycinnamic acid), H (glyinflanin A), and J (3-deshydroxysappanol trimethyl ether), yielded the best docking scores with respect to the target proteins, of which three (E (4-hydroxycinnamic acid), H (glyinflanin A), and J (3-deshydroxysappanol trimethyl ether)) were identified to have relatively optimal drug-likeness and medicinal chemistry characteristics. Thus, the present study concluded that these compounds may have contributed to the observed antidiabetic properties of these plants and can be investigated further as drugs or drug-like compound candidates.

In silico identification and study of potential anti-mosquito juvenile hormone binding protein (MJHBP) compounds as candidates for dengue virus - Vector insecticides

“…The control ligands were imported into the query ligand databases prior to preparation and docking. The database of ligand/control structures was prepared for docking as follows in MOE: protonation at a temperature of 300 K and pH 7.0 and energy minimization, using default parameters - Amber10-EHT force field was used with no periodicity, the constraints were maintained at the rigid water molecule level and partial charges were also applied [ 27 , 28 ].

Fig.

…”

“…The preparatory process included removal of water molecules and other co-crystalized molecules, protonation, partial charges and energy minimization were implemented as described above in ligand preparation. The fully prepared and optimized 3D structure was saved in moe format for docking [ [27] , [28] ].…”

“…The protein-ligand docking poses and scores were saved in db format and ligand interaction with protein visualized (2D and 3D) using Discovery studio and MOE-ligand interaction options. The results of the top-ranking compounds were presented in tables and figures [ [27] , [28] ].…”

Phytochemical Characterization, Functional Nutrition, and Anti-Diabetic Potentials of Leptadenia hastata (pers) Decne Leaves: In Silico and In Vitro Studies

“…The high GIA of these compounds is of immense therapeutic benefit in DM because they are required to reduce postprandial glucose levels by inhibiting the activities of α-amylase and α-glucosidase in the gastrointestinal tract (GIT). 57 However, rutin with low GIA could work by other mechanisms and be administered via other routes such as para-cellular diffusion, passive, lipoidal diffusion, and uptake by transporter protein. 58 Importantly, rutin being a substrate to P-glycoprotein, an ATP-binding transmembrane glycoprotein responsible for active efflux of drugs and other chemicals out of the cells 57 suggests a promising hindrance of rutin toxicity elevation.…”

“… 57 However, rutin with low GIA could work by other mechanisms and be administered via other routes such as para-cellular diffusion, passive, lipoidal diffusion, and uptake by transporter protein. 58 Importantly, rutin being a substrate to P-glycoprotein, an ATP-binding transmembrane glycoprotein responsible for active efflux of drugs and other chemicals out of the cells 57 suggests a promising hindrance of rutin toxicity elevation.…”