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Direct unimolar one-step valeroylation of methyl α- d -mannopyranoside (MDM) furnished mainly 6- O -valeroate. However, similar reaction catalyzed by DMAP resulted 3,6-di- O -valeroate (21%) and 6- O -valeroate (47%) indicating reactivity sequence as 6-OH>3-OH>2-OH,4-OH. To get potential antimicrobial agents, 6- O -valeroate was converted into four 2,3,4-di- O -acyl esters, and 3,6-di- O -valeroate was converted into 2,4-di- O -acetate. Direct tetra- O -valeroylation of MDM gave a mixture of 2,3,4,6-tetra- O -valeroate and 2,3,6-tri- O -valeroate indicating that the C2–OH is more reactive than the equatorial C4–OH. The activity spectra analysis along with in vitro antimicrobial evaluation clearly indicated that these novel MDM esters had better antifungal activities over antibacterial agents. In this connection, molecular docking indicated that these MDM esters acted as competitive inhibitors of sterol 14α-demethylase (CYP51), an essential enzyme for clinical target to cure several infectious diseases. Furthermore, pharmacokinetic studies revealed that these MDM esters may be worth considering as potent candidates for oral and topical administration. Structure activity relationship (SAR) affirmed that saturated valeric chain (C5) in combination with caprylic (C8) chains was more promising CYP51 inhibitor over conventional antifungal antibiotics.

Alzheimer disease (AD) can be considered the most common age-related neurodegenerative disorder, and also, an important cause of death in elderly patients. A number of studies found the correlation of this disease pathology with BACE1 inhibitor and it is also evident that BACE1 inhibitor can function as a very potent treatment strategy in treating AD. In the present study, we aimed to prospect for novel plant-derived BACE1 inhibitors from Leea indica and to realize the structural basis of their interactions and mechanisms using combined molecular docking and molecular dynamics based approaches. An extensive library of Leea indica plant-derived molecule was compiled and computationally screened for inhibitory action against BACE1 by using virtual screening approaches. Furthermore, induced fit docking and classical molecular dynamics along with steered molecular dynamics simulations were employed to get insight the binding mechanisms. Two triterpenoids, ursolic acid and lupeol were identified through virtual screening; wherein, lupeol showed better binding free energy in MM/GBSA, MM/PBSA and MM/GBVI approaches. Furthermore classical and steered dynamics revealed the favourable hydrophobic interactions between the lupeol and the residues of flap or catalytic dyad of BACE1; however, ursolic acid showed disfavorable interactions with the BACE1. This study, therefore, unveiled the lupeol as a potent BACE1 inhibitor from a manually curated dataset of Leea indica molecules, which may provide a new dimension of designing novel BACE1 inhibitors for AD therapy.

Background:: Adhatoda vasica (Nees.) of 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 and 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 were collected from various resources including books, review papers, research papers and reports which were obtained by an online search of worldwide-accepted scientific databases. ChemDraw software was used to draw the compounds’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 phytopharmaceutical potential agent that exhibits diverse pharmacological activities including antibacterial, antifungal, hepatoprotective, anti-ulcer, abortifacient, antiviral, anti-inflammatory, thrombolytic, hypoglycemic, anti-tubercular, antioxidant and antitussive activities. Conclusions: The sufficient number of studies on ethno-pharmacology, 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.

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