In vitro activity of synthetic tetrahydroindeno[2, 1-c]quinolines on Leishmania mexicana. Issue 6 (December 2015)

• Record Type: Journal Article
• Authors: Hernández-Chinea, Concepción; Carbajo, Erika; Sojo, Felipe; Arvelo, Francisco; Kouznetsov, Vladimir V.; Romero-Bohórquez, Arnold R.; Romero, Pedro J.
• Is Part Of: Parasitology international. Volume 64:Issue 6(2015:Dec.)
• Page Start: 479
• Page End: 483
• Publication Date: 2015-12
• Subjects: Leishmania mexicana -- Promastigote -- Indenoquinoline -- Antileishmanial drugs; Parasitology -- Periodicals; Parasites -- Periodicals; Parasitic Diseases -- Periodicals; Parasitology -- Periodicals; Parasitologie -- Périodiques; 571.99905
• DOI: 10.1016/j.parint.2015.06.011
• Languages: English
• ISSNs: 1383-5769

Abstract

Abstract: New synthetic compounds based on tetrahydroindenoquinoline structure were evaluated for their in vitro antileishmanial activities. The seven compounds assayed have antiproliferative activities against promastigotes of Leishmania mexicana . Compound1 and3 were the most active (IC50 1.0 μg/ml) and showed high selectivity towards the parasite. These compounds were selected to evaluate their effect on promastigote morphology and mitochondrial transmembrane potential as well as on the amastigote capability to survive into macrophages J774 cell line. Whereas compound1 affected the promastigote cell cycle, compound 3 induced morphological changes and the total collapse of the mitochondrial transmembrane potential, a hallmark of apoptosis. Both compounds also affected the amastigote form of the parasite, decreasing their survival rate in J774 macrophages. Due to the greatest selectivity index, the apparent effect as apoptotic inducer and its sustained inhibition on intracellular amastigote replication, compound3 is the best candidate to be tested in vivo. This compound is worth considering for the development of new antileishmanial drugs. Graphical abstract: Highlights: Antileishmanial activity of synthetic tetrahydroindeno [2, 1-c]quinolines was evaluated in vitro. Compounds were active against promastigotes of Leishmania mexicana . Two of the most active compounds (1 and3 ) impair amastigote survival in macrophages. Results indicate that compound3 is the best candidate for development of antileishmanial drugs.