Structure activity relationship, acute toxicity and cytotoxicity of antimycobacterial neolignan analogues

Abstract

LS-2 (1) showed promising antimycobacterial activity and very weak cytotoxicity in cell culture, as well as an absence of toxicity in primary culture of hepatocytes. In the acute toxicity study there was an indication of absence of toxicity on murine models, in vivo.

Effects of the antimycobacterial compound 2-phenoxy-1-phenylethanone on rat hepatocytes and formation of metabolites

“…These data support previous data for LS-2 in mammalian cells, i.e., J774 macrophages, V79 cells and rat hepatocytes, in which very low or no cytotoxicity of LS-2 was observed. Additionally, a previous study showed that LS-2 induced acute toxicity in mice only at a high dose of 1.87 g/kg (De Souza et al, 2011). In accordance with previous results, all the data obtained suggest no toxicity of LS-2 or its metabolites against rat hepatocytes, which is a good indication of a lack of side effects of a drug during treatment.…”

“…The most effective analogue, 2-phenoxy-1-phenylethanone (LS-2), showed promising extra-and intracellular antimycobacterial activity and very weak cytotoxicity against V79 cells, J774 macrophages and rat hepatocytes. Additionally, in mice, the lethal dose (LD 50 ) was found to be high, i.e., 1.87 g/kg (De Souza et al, 2011).…”

“…Natural neolignans have been isolated from Virola surinamensis and found to be effective against Schistosoma mansoni (Barata et al, 1978). In studies covering infectious diseases, neolignan analogues were synthesized (Barata et al, 1978;Aveniente et al, 2007) and shown to have antimicrobial activity against Leishmania (Barata et al, 2000), Schistosoma (Alves et al, 2002), fungi (Lima et al, 1987) and Mycobacterium tuberculosis H37Rv (De Souza et al, 2011). The most effective analogue, 2-phenoxy-1-phenylethanone (LS-2), showed promising extra-and intracellular antimycobacterial activity and very weak cytotoxicity against V79 cells, J774 macrophages and rat hepatocytes.…”

Computational modelling of the antischistosomal activity for neolignan derivatives based on the MIA-SAR approach

“…The neolignans are dimers formed from oxidative coupling of allyl and propenil phenols that occur in the Myristicaceae family of plants. The neolignans employed in this paper are those of the type 8.O.4′, with an O bridge between carbons 8 and 4 [20], where five have been reported to be active (5,6,8,9,17) and 13 are reported to be inactive (1,2,3,4,7,10,11,12,13,14,15,16,18) to S. mansoni.…”

“…In a previous study on phytochemicals of therapeutic interest, it was shown that neolignans extracted from leaves of the plant Virola surinamensis exhibit biological activity against several microorganisms, such as bacteria [7], fungi [8] and other parasites, such as Leishmania spp. [9,10] Trypanosoma cruzi [11] and S. mansoni [12,13].…”