Synthesis and preliminary antimicrobial analysis of Isatin-ferrocene and Isatin-ferrocenyl-chalcone conjugates

Authors: SINGH, AMANDEEP - Guru Nanak Dev University; FONG, GRANT - University Of The Pacific; LIU, JENNY - University Of The Pacific; WU, YUN-HSUAN - University Of The Pacific; CHANG, KEVIN - University Of The Pacific; PARK, WILLIAM - University Of The Pacific; KIM, JIHWAN - University Of The Pacific; Tam, Christina; Cheng, Luisa; LAND, KIRKWOOD - University Of The Pacific; KUMAR, VIPAN - University Of The Pacific

Submitted to: ACS Omega
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/17/2018
Publication Date: 5/30/2018
Publication URL: https://handle.nal.usda.gov/10113/6473320
Citation: Singh, A., Fong, G., Liu, J., Wu, Y., Chang, K., Park, W., Kim, J., Tam, C.C., Cheng, L.W., Land, K.M., Kumar, V. 2018. Synthesis and preliminary antimicrobial analysis of Isatin-ferrocene and Isatin-ferrocenyl-chalcone conjugates. ACS Omega. 3(5):5808-5813. https://doi.org/10.1021/acsomega.8b00553.
DOI: https://doi.org/10.1021/acsomega.8b00553

Interpretive Summary: Discovering and designing new therapies against infectious diseases is critical to human and animal health, especially in light of increases in drug resistance of many pathogens. Here, we synthesized a new set of isatin-conjugates compounds with unique chemical compositions and tested them against a mucosal protozoal pathogen–Trichomonas vaginalis. Several lead compounds with increased efficacy from previously identified drugs were identified. Since antibiotics often negatively impact the normal flora of a patient, we also screened the chemical library on several known normal flora bacteria and observed no effect on their growth at the highest concentration used in this study. Taken together, this study shows that several of these compounds could be possible new drug leads against mucosal pathogens.

Technical Abstract: In this study, we outline the synthesis of isatin-ferrocenylchalcone and 1H- 1, 2, 3 - triazole tethered isatin-ferrocene conjugates along with their antimicrobial evaluation against the human mucosal pathogen Trichomonas vaginalis. The introduction of triazole ring among the synthesized conjugates improved the activity profiles with most of the compounds in the library, exhibiting 100% growth inhibition in a preliminary susceptibility screen at 100 µM. IC50 determination of the most potent compounds in the set revealed an inhibitory range between 2-13 µM. Normal flora microbiome are unaffected by these compounds, suggesting these may be new chemical scaffolds for discovery of new drugs against trichomonad infections.