The Antileishmanial Potential of C-3 Functionalized Isobenzofuranones against Leishmania (Leishmania) Infantum Chagasi

Abstract

Leishmaniases are diseases caused by protozoan parasites of the genus Leishmania. Clinically, leishmaniases range from cutaneous to visceral forms, with estimated global incidences of 1.2 and 0.4 million cases per year, respectively. The treatment of these diseases relies on multiple parenteral injections with pentavalent antimonials or amphotericin B. However, these pharmaceuticals are either too toxic or expensive for routine use in developing countries. These facts call for safer, cheaper, and more effective new antileishmanial drugs. In this investigation, we describe the results of the assessment of the activities of a series of isobenzofuran-1(3H)-ones (phtalides) against Leishmania (Leishmania) infantum chagasi, which is the main causative agent of visceral leishmaniasis in the New World. The compounds were tested at concentrations of 100, 75, 50, 25 and 6.25 µM over 24, 48, and 72 h. After 48 h of treatment at the 100 µM concentration, compounds 7 and 8 decreased parasite viability to 4% and 6%, respectively. The concentration that gives half-maximal responses (LC 50 ) for the antileishmanial activities of compounds 7 and 8 against promastigotes after 24 h were 60.48 and 65.93 µM, respectively. Additionally, compounds 7 and 8 significantly reduced parasite infection in macrophages.

Green Synthesis: A Novel Method for Bromination of 7-AminoPhthalide

“…Finally, the temperature factor is significant since at 100 o C, irrespective of halogenated substrates, the intermediate phthalides 2a, 2e and 2j (not isolated) is formed, and whereas at 170 o C, formation of halide substituted 7-amino phthalide is depends on halogenated substrate. Bromine as external source: Independently, the 7-Amino phthalide (2a and 2e), and its sulfonated substrate (16) on treatment (table-3) with 1.0 eq of bromine in conc sulfuric acid at 100 o C obtains the mono brominated 7-Aminophthalides (3a and 3e), this is due to availability of bromonium ion by cleavage of bromine molecules, whereas at 170 o C as expected we isolated the dibromo derivatives 4a and 4e respectively. These products (4a and 4e) The reaction is exceptionally clean and easy workup is required to obtained spectrally pure substances.…”

Green Synthesis: A Novel Method for Bromination of 7-AminoPhthalide

“…Bromine as external source: Independently, the 7-Amino phthalide (2a and 2e), and its sulfonated substrate(16) on treatment (table-3) with 1.0 eq of bromine in conc sulfuric acid at 100 o C obtains the mono brominated 7-Aminophthalides (3a and 3e), this is due to availability of bromonium ion by cleavage of bromine molecules, whereas at 170 o C as expected we isolated the dibromo derivatives 4a and 4e respectively. These products (4a and 4e) formation further suggest bromide ion is oxidized to bromine/bromonium ion in conc sulfuric acid at 170 o C and facilitate electrophilic bromination.…”

The therapeutic potential of novel isobenzofuranones against Naegleria fowleri

“…Previous studies have shown several biological properties of these molecules such as antibacterial ( Rahman et al, 2005 ), antitumoral ( Da Silva Maia et al, 2016 ; Logrado et al, 2010 ; Teixeira et al, 2013 ) and antifungal activities ( Sánchez-Fernández et al, 2020 ; Strobel et al, 2002 ). In addition, a recent study in Leishmania genus, a parasitic protozoan, showed the activity of isobenzofuranones against this pathogen( Mishra et al, 2014 ; Pereira et al, 2015 ).…”