The discovery of antioxidants in marine microorganisms and their protective effects on the hepatic cells from chemical-induced oxidative stress.

The marine environment is emerging as a biodiversity resource for the discovery of natural molecules or chemical scaffolds with pharmaceutical activity. Marine microbes have a tremendous ability to sense and respond to their surroundings to survive in a stressful environment by producing different molecules. As oxidative stress is directly or indirectly involved in various pathological conditions in humans, we believe that marine-derived antioxidant molecules will have a great prospect as a novel antioxidant molecule. We, in this work, explored the marine microbial resources from the Gulf of Mannar, Bay of Bengal, India. High-throughput screening of antioxidant molecule producing marine microbes has revealed that extract from Kocuria marina CDMP 10, can effectively reduce the DPPH free radical. Methanolic crude extract obtained by the freeze-thawing was fractionated and purified by using activity guided purification with the help of reverse phase HPLC and analysed through UPLC-MS. Chemical analysis, as well as MS-spectra, indicated that marine bacteria K. marina CDMP 10 derived antioxidant fraction contains the short peptides. The antioxidant activity of the three highly hydrophobic peptides, (Ser-Ser-Gln, Phe-Glu, Asp-Ile and Leu-Glu) was confirmed by in vitro as well as a cell-based assay. These small peptide molecules are noncytotoxic and can prevent the human cells from chemical-induced oxidative stress. Ser-Ser-Gln peptide demonstrated a potent free radical scavenging activity in Hepatocellular carcinoma cell lines. This study suggests that these short peptides from K. marina CDMP 10 may serve as a potential pharmaceutical candidate with antioxidant activity.

Synthesis and antimicrobial evaluation of piperic acid amides and their lower homologues.

Seven piperic acid amides along with their lower homologs (12) were synthesized using HATU-DIPEA coupling reagent. All the synthesized derivatives were evaluated for their antibacterial activities against Staphylococcus aureus, Pseudomonas aeruginosa, and vancomycin-resistant P. aeruginosa. They were found to be more active on P. aeruginosa than on S. aureus. However, they did not exhibit potent activity on Vancomycin resistant P. aeruginosa. Among the tested compounds, methylenedioxycinnamic acid amide of anthranilic acid (MDCA-AA, 2a) was found to be most active against S. aureus with MIC of 3.125 µg/ml. The PAS and INH amides of piperic acid were screened against Mycobacterium tuberculosis H37Ra strain. They were found to be most active among all the tested compounds but were found to be less active than the standard drug, isoniazid.

In-house chemical library repurposing: A case example for Pseudomonas aeruginosa antibiofilm activity and quorum sensing inhibition.

Hit, Lead & Candidate Discovery Drug repurposing has become a recent trend in drug development programs, where previously developed drugs are explored for hit and redeveloped into potential therapeutic agents for new diseases. Globally, in any drug development program, a series of molecules are synthesized and evaluated for the hypothesized activity. Hits are developed into lead molecules or drugs, whereas the negative ones are shelved in the lab with no immediate use. We in this project took the previously sidelined small chemical molecules to the next level of utility, where previously developed in-house small molecules library are tested for the unexplored biological relevant activity. As biofilm formation and quorum sensing play a vital role in bacterial pathogenesis, we believe that they could be one of the most effective targets for antimicrobial agents. In this study, we report the evaluation of 50 different compounds for anti-biofilm and anti-quorum sensing activity against Pseudomonas aeruginosa. Out of the screened compounds, three hydrazine-carboxamide hybrid derivatives showed promising anti-biofilm property and inhibition of pyocyanin production without any direct antimicrobial activity and cytotoxicity issues. Hydrazine-carboxamide hybrids can be a new class and promising leads for further anti-biofilm and anti-virulence development against microbial infections.