Greener approach for the isolation of oleanolic acid from Nepeta leucophylla Benth. Its derivatization and their molecular docking as antibacterial and antiviral agents

In the present study bioactive methanolic extract along with chloroform and hexane extracts obtained from shade dried leaves of the Himalayan aromatic medicinal plant Nepeta leucophylla Benth. Were screened for the presence of triterpenoids, especially oleanolic acid (OA). Total three compounds oleanolic acid, squalene and linoleic methyl ester were isolated from methanol extract. The percentage yield of OA was 0.11%. Out of these three, OA is more bioactive and was further subjected to derivatization using greener Ultrasonication method. Total three derivatives (3-Acetyl oleanolic acid, 3-Phthaloyl oleanolic acid and 3-Oxo oleanolic acid) were synthesized with 91.16%, 93.98%, and 83.6% respectively. Further, the antioxidant potential of OA and its derivatives were evaluated using DPPH assay which suggested that the 3-Phthaloyl oleanolic acid exhibits highest antioxidant potential with 40.83 ± 1.14% inhibition. OA and its derivatives were screened in-silico antibacterial potential against three bacterial pathogens (E-coli, M. tuberculosis and S. aureus) and antiviral potential against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), Human immunodeficiency virus (HIV) and H1N1 influenza virus. The in-silico results suggested that 3-phthaloyl oleanolic acid showed best H-bonding with FtsA (Staphylococcus aureus), enoyl acyl reductase (E. coli) and arabinosyl transferase (Mycobactrium tuberculosis). 3-Phthaloyl oleanolic acid also showed best H-Bond interactions with the target proteins hemagglutinin (H1N1) and reverse transcriptase (HIV), whereas, oleanolic acid exhibited the best interactions with RNA dependent RNA polymerase (SARS-CoV-2) and thus could be considered for further in vitro studies.