Repurposing of existing antibiotics for the treatment of diabetes mellitus.

Proline specific serine protease enzyme, dipeptidyl peptidase IV (DPP-4) has become a promising target for diabetes, as it stops glucagon-like peptide 1 (GLP-1) from becoming inactive, resulting in higher levels of active GLP-1. This lowers glucose levels by increasing insulin secretion and decreasing glucagon secretion. DPP-4 is also linked to a higher BMI and a 0.7 to 1% reduction in HbA1c. Currently available DPP-4 inhibitor drugs showed less promising anti-diabetic activity as this class associated with many side effects due to non-selectivity and therefore searching on more potent DPP-4 inhibitors are still ongoing. In our present study, we investigate the inhibition of DPP-4 through a series of antibiotic compounds which were previously reported to be used in diabetic foot infections and compared with existing DPP-4 inhibitors. To obtain this objective, three-dimensional crystal structure of DPP-4 was retrieved from the protein data bank (PDB id: 1 × 70). A systematic computational method combining molecular docking, MM-GBSA binding energy calculation, MD simulations, MM-PBSA binding free energy calculations and ADME were used to find best DPP-4 inhibitor. Molecular docking results revealed that clindamycin has a higher affinity towards the catalytic sides of DPP-4 and built solid hydrophobic and polar interactions with the amino acids involved in the binding region of DPP-4, such as S1 subsite, S2 subsite and S2 extensive subsite. MD simulations results showed clindamycin as potent virtual hit and suggested that it binds with DPP-4 in competitive manner, which virtually indicate that besides antibiotic activity clindamycin has anti-diabetic activity. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-021-00118-6.

Adhatoda vasica (Nees.): A Review on its Botany, Traditional uses, Phytochemistry, Pharmacological Activities and Toxicity.

BACKGROUND: Adhatoda vasica (Nees.) of the family Acanthaceae has been used in the Southeast tropical zone as it is efficacious against headache, colds, cough, whooping cough, fever, asthma, dyspnea, phthisis, jaundice, chronic bronchitis, and diarrhea. It exhibits commendable pharmacological activities. OBJECTIVE: The aim of the review is to provide a systematic overview of pharmacological activities with toxicity and clinical assessment, phytochemistry of A. vasica along with its characterization, geographical observation, phenology, traditional uses, as well as an organized representation of the findings. METHOD: The overall information of A. vasica was collected from various resources, including books, review papers, research papers, and reports which were obtained from an online search of globallyaccepted scientific databases. ChemDraw software was used to draw the compound's structure. RESULTS: Phytochemical review on A. vasica has led to the collection of 233 compounds of different types such as alkaloids, flavonoids, essential oils, terpenoids, fatty acids, phenols, etc. It is a promising source of potential phytopharmaceutical agent that exhibits diverse pharmacological activities, including antibacterial, antifungal, hepatoprotective, anti-ulcer, abortifacient, antiviral, antiinflammatory, thrombolytic, hypoglycemic, anti-tubercular, antioxidant, and antitussive activities. CONCLUSIONS: Sufficient number of studies on ethnopharmacology, traditional uses, and pharmacological activities of A. vasica are conducted. Furthermore, it is necessary to study the activity of chemical constituents for new drug design and discovery from natural products.