title: β-Nitrostyrenes as Potential Anti-leishmanial Agents.
abstract: Development of new therapeutic approach to treat leishmaniasis has become a priority. In the present study, the antileishmanial effect of β-nitrostyrenes was investigated against in vitro promastigotes and amastigotes. A series of β-nitrostyrenes have been synthesized by using Henry reaction and were evaluated for their antimicrobial activities by broth microdilution assay and in vitro antileishmanial activities against Leishmania donovani promastigotes by following standard guidelines. The most active compounds were futher evaluated for their in vitro antileishmanial activities against intracellular amastigotes. Among the tested β-nitrostyrenes, compounds 7, 8, 9, 12, and 17 exhibited potential activities (MICs range, 0.25-8 μg/mL) against clinically significant human pathogenic fungi. However, the microbactericidal concentrations (MBCs) and the microfungicidal concentrations (MFCs) were found to be either similar or only two-fold greater than the MICs. Anti-leishmanial results demonstrated that compounds 9, 12, 14, and 18 were found to be most active among the tested samples and exhibited 50% inhibitory concentration (IC50) by 23.40 ± 0.71, 37.83 ± 3.74, 40.50 ± 1.47, 55.66 ± 2.84 nM against L. donovani promastigotes and 30.5 ± 3.42, 21.46 ± 0.96, 26.43 ± 2.71, and 61.63 ± 8.02 nM respectively against intracellular L. donovani promastigotes amastigotes respectively which are comparable with standard AmB (19.60 ± 1.71 nM against promastigotes and 27.83 ± 3.26 nM against amastigotes). Compounds 9, 12, 14, and 18 were found to have potent in vitro leishmanicidal activity against L. donovani and found to be non-toxic against mammalian macrophages even at a concentration of 25 μM. Nitric oxide (NO) estimation studies reveals that these compounds are moderately inducing NO levels.
authors.affiliation: Medicinal Chemistry Lab, Department of Chemistry, Faculty of Science, Hamdard University New Delhi, India.
authors.forename: Syed
authors.initials: S
authors.lastname: Shafi
authors.affiliation: Department of Medical Laboratories Technology, Faculty of Applied Medical Sciences, Taibah UniversityMedina, Saudi Arabia; Parasite Immunology Lab, Department of Biotechnology, Faculty of Science, Hamdard UniversityNew Delhi, India.
authors.forename: Farhat
authors.initials: F
authors.lastname: Afrin
authors.affiliation: Parasite Immunology Lab, Department of Biotechnology, Faculty of Science, Hamdard UniversityNew Delhi, India; Molecular Virology and Vaccinology Lab, Department of Biotechnology, Faculty of Science, Hamdard UniversityNew Delhi, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Islamuddin
authors.affiliation: Parasite Immunology Lab, Department of Biotechnology, Faculty of Science, Hamdard University New Delhi, India.
authors.forename: Garima
authors.initials: G
authors.lastname: Chouhan
authors.affiliation: Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University New Delhi, India.
authors.forename: Intzar
authors.initials: I
authors.lastname: Ali
authors.affiliation: Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard New Delhi, India.
authors.forename: Faatima
authors.initials: F
authors.lastname: Naaz
authors.affiliation: Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard New Delhi, India.
authors.forename: Kalicharan
authors.initials: K
authors.lastname: Sharma
authors.affiliation: Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard New Delhi, India.
authors.forename: Mohammad S
authors.initials: MS
authors.lastname: Zaman
keywords: antimicrobicidal; leishmanicidal; macrophages; promastigotes; β-nitrostyrenes