Inhibitory Action of Gossypol on Enzymes and Growth of Trypanosoma cruzi

Abstract

Gossypol, a phenolic compound isolated from the cotton plant, is a powerful inhibitor of nicotinamide adenine dinucleotide-linked enzymes (alpha-hydroxyacid dehydrogenase and malate dehydrogenase) of Trypanosoma cruzi, the parasite that causes Chagas' disease. Parasites at the epimastigote stage that were incubated for 5 minutes with 100 micromolar gossypol were completely immobilized. Concentrations of gossypol as low as 0.01 micromolar markedly reduced the growth rate of T. cruzi in culture.

Gossypol binds to a high‐affinity binding site on human serum albumin

“…Clinical trials in China suggest that gossypol is an effective, non-steroidal, antifertility drug for men [2,3]. In addition, reports have appeared recently on the potential usefulness of gossypol as a drug against herpes simplex virus [4], Chagas disease [5] and malaria [6]. In view of the potential broad spectrum activity of gossypol as a drug, knowledge of the transport and metabolism of gossypol will be useful.…”

Trypanosoma cruzi: inhibition of alpha-hydroxyacid dehydrogenase isozyme II by N-allyl and N-propyl oxamates and their effects on intact epimastigotes

“…In addition, HADHisozyme II it is also an isozyme that participates in the reoxidation of NADH during glycolysis (Coronel et al 1981). According to this, isozyme II is the isozyme that it is actually integrated in metabolic pathways supplying energy for motility and survival of the parasite (Montamat et al 1987), and therefore, it has been proposed that inhibitors of this isozyme could reduce the motility and survival of this parasite (Montamat et al 1982, Gerez de Burgos et al 1984). …”

“…Recently, the glycolytic enzymes have been suggested as a possible target for anti-trypanosomatid drugs design (Bakker et al 2000, Verlinde et al 2001, Lakhdar-Ghazal et al 2002, because glycolysis provides virtually all the energy for the bloodstream form of trypanosomatids (Michels 1988, Wang 1995, Bakker et al 2000. T. cruzi HADH-isozyme II is an important isozyme due to its participation in the energy metabolism of the parasite and therefore, it has been proposed that inhibitors of this enzyme could reduce the motility and survival of this parasite (Montamat et al 1982, Gerez de Burgos et al 1984, Nogueda et al 2001.…”

Synthesis and Anti-Tumor Activities of Fluoride-Containing Gossypol Derivatives Compounds

“…Up to now, gossypol has been showed to exhibit anti-tumor activities towards a wide range of tumors, such as Ehrlich ascites tumor cells [2], SW-13 adrenocortical carcinoma cells [3], hormone-dependent and hormone-independent breast carcinoma [4,5], colon carcinoma cell line HT-29 and LoVo [6], human pancreatic cancer cell line [7], prostate cancer cell lines [8], head and neck cancer cells [9,10]. In addition, many synthesized gossypol derivatives and analogues possess disease-inhibiting activities [11], as anti-parasitic [12,13], anti-malarial [14][15][16], anti-HIV [17][18][19] and anticancer [20][21][22][23]. Derivatives such as gossypol Schiff bases prepared by modifying gossypol's aldehyde groups were supposed to Open Access Natural Science reduce its host toxicity ( Figure 1) while retaining or enhancing its therapeutic effects [24].…”