title: New flavonol methyl ether from the leaves of Vitex peduncularis exhibits potential inhibitory activity against Leishmania donovani through activation of iNOS expression.
abstract: One new flavonol methyl ether (1), along with four known compounds from the leaves of methanol extract of Vitex peduncularis Wall and three known compounds from the leaves of methanol extract of Vitex pinnata Linn (Verbenaceae) were isolated. The chemical structure of the new compound was established by detailed spectroscopic studies. The in vitro antileishmanial activities of 1 against both Leishmania donovani promastigote and amastigote forms were evaluated. To characterize the effector mechanism of compound 1 against Leishmania parasite infected THP-1 macrophage cells, RT-PCR analysis of inducible nitric oxide synthase 2 (iNOS2) was done followed by measurement of nitric oxide generation by Griess reaction. Pentostam (sodium antimonygluconate) was used as reference drug. Compound 1 exhibited better antileishmanial activity than sodium antimonygluconate (SAG) (having IC50 values for promastigote, 2.4 and 58.5 μM and for amastigotes, 0.93 and 36.2 μM, respectively). Compound 1 was less toxic than SAG towards THP-1 having CC50 of 123.7 μM and 364.3 μM, respectively. Moreover, compound 1 was found to induce a potent host-protective response by enhancing NO generation and iNOS2 expression in infected macrophages to prevent the progression of Leishmania parasite.
authors.affiliation: Department of Chemistry, Tripura University, Suryamaninagar 799022, Tripura, India.
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Rudrapaul
authors.affiliation: Department of Chemistry, Tripura University, Suryamaninagar 799022, Tripura, India.
authors.forename: Indrajit Sil
authors.initials: IS
authors.lastname: Sarma
authors.affiliation: Department of Chemistry, Netaji Subhas Mahavidyalaya, Udaipur 799114, Gomati Tripura, India.
authors.forename: Niranjan
authors.initials: N
authors.lastname: Das
authors.affiliation: Department of Chemistry, Tripura University, Suryamaninagar 799022, Tripura, India.
authors.forename: Utpal Chandra
authors.initials: UC
authors.lastname: De
authors.affiliation: Department of Molecular Biology and Bioinformatics, Tripura University, Suryamaninagar 799022, Tripura, India.
authors.forename: Surajit
authors.initials: S
authors.lastname: Bhattacharjee
authors.affiliation: Department of Chemistry, Tripura University, Suryamaninagar 799022, Tripura, India. Electronic address: dindabtu@gmail.com.
authors.forename: Biswanath
authors.initials: B
authors.lastname: Dinda
mesh_terms: D002460:Cell Line; D044948:Flavonols / Q000737:chemistry* / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000469:parasitology; D007893:Leishmania donovani / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology; D008738:Methyl Ethers / Q000737:chemistry; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D009573:Nitrites / Q000378:metabolism; D018515:Plant Leaves / Q000737:chemistry*; D020950:Vitex / Q000737:chemistry*
chemical_list: D044948:Flavonols; D008738:Methyl Ethers; D009573:Nitrites; D052247:Nitric Oxide Synthase Type II
keywords: Antiproliferative; Flavonoids; Leishmania donovani; Vitex peduncularis; Vitex pinnata