Trypanocidal constituents in plants: 7. Mammea-type coumarins

Abstract

The protozoan Trypanosoma cruzi is the etiological agent of Chagas disease (American trypanosomiasis), which affects 16-18 million people in Latin America and is responsible for the deaths of more than 45,000 patients per year (WHO 1997). It is transmitted to humans by triatomine bugs or through infected blood transfusions (Pizzolatti et al. 2002). The life cycle of T. cruzi is complex, and it alternates between vertebrate and invertebrate hosts. When the triatomine bug is feeding on human blood, it defecates and releases metacyclic trypomastigotes near the bite wound. This infective agent is capable of reaching intracellular locations and transforming into amastigotes. After reproduction, the amastigotes turn back into trypomastigotes, and the cells burst. The released parasites can either infect other cells or be consumed by other triatomine bugs. In the intestine of an invertebrate host, the blood trypomastigotes transform into epimastigotes, which divide and give rise to infective metacyclic-trypomastigotes (Brener 1973, Contreras et al. 2002.Medication for Chagas disease is usually effective when given during the acute stage of infection. Once the disease has progressed to later stages, no medication has proven to be completely effective. Moreover, synthetic drugs such as nifurtimox, a 5-nitrofuran, and benznidazole, a 2-nitro-imidazole (Lampit®, Bayer, and Rochagan®, Roche, respectively) are used for the treatment of this disease. Unfortunately, both drugs have limited efficacy during the chronic phase of the disease and present several undesirable side effects (Gutteridge 1985, Umezawa et al. 2001, Coura & Castro 2002. Chemoprophylatic measures against Chagas disease are scarce, present variable efficacy, or are not adopted due to their costs. Currently, gentian violet is used to sterilize blood banks in endemic areas (Pizzolatti et al. 2002, Coura & Castro 2002). An urgent need to develop new drugs exists, and natural products can provide useful drug leads as well as the scientific basis for the rational use of medicinal plants.Calophyllum brasiliense Camb. is a large tree, measuring up to 40 m in height, from the tropical rain forest. It is distributed throughout Latin America, from Brazil to Mexico, and is used in folk medicine. In Mexico, its most common name is bari, and the infusion of the cortex is consumed by women over nine days for "cleaning" the womb after child-birth, while the seeds provide an oil used for lighting and for healing skin afflictions (Soto & Sousa 1995). In Colombia, the peasants call this tree ár-bol de aceite (oil tree), and the yellow latex exuded from the cortex is applied topically for healing the navels of newborn children (García-Barriga 1992). In Brazil, it is known as guanandi, and has been used in folk medicine for the treatment of rheumatism, varicose hemorrhoids and chronic ulcers (Corrêa 1978). In the Amazon basin, the bark infusion is used by the Karaja ethnic group for the treatment of diarrhea, and in Guyana, C. brasiliense is mixed with Coutarea hexandra to trea...

Synthesis and Trypanocidal Properties of New Coumarin-Chalcone Derivatives

“…Coumarins are a family of natural and/or synthetic compounds with different pharmacological activities [10,11], being one of them the antiparasitic activity [12,13]. Some coumarins proved to be important molecules in the regression of the described pathology.…”

Soulamarin Isolated from Calophyllum brasiliense (Clusiaceae) Induces Plasma Membrane Permeabilization of Trypanosoma cruzi and Mytochondrial Dysfunction

“…xantones, flavonoids, triterpenoids, and coumarins [2]. Some coumarins isolated from C. brasiliense displayed trypanocidal activity, but unfortunately, no information about the underlying mechanism was available [3].…”

Synthesis of a New Series of Amino Acid Derivatives of Substitiuted Coumarin and Its Antimicrobial Activity Applications

“…More recently, specific studies looking at the effects of coumarins as a cytochrome P-450 inhibitor which is a carcinogen metabolizing enzyme (15) . Coumarins have also been found to have beneficial effects on malaria (16) . Based on the biological importance of several coumarins (17,18) and in continuation of our work on the structure-activitry corelation in a variety of amino acid derivatives (19)(20)(21)(22) , we undertook the synthesis of a new series of coumarin and benzocoumarin derivatives incorporating with amino acid moieties to evaluate the antimicrobial activity.…”