A Novel and Potent Antileishmanial Agent: In Silico Discovery, Biological Evaluation, and Analysis of Its Structure-Activity Relationships

摘要

Leishmaniasis, a disease caused by protozoan parasites of the genus Leishmania, currently afflicts 12 million people worldwide, with 2 million new cases occurring annually. Without effective treatment, visceral leishmaniasis is associated with a near 100% fatality rate, while other forms can be severely disfiguring and debilitating. Novel therapies are urgently needed to treat this disease, as current treatments possess negative attributes such as toxicity, expense, inconvenience, and loss of effectiveness due to resistance. Research efforts directed by Karl Werbovetz have previously demonstrated the promising antileishmanial activity of several dinitroaniline sulfonamide compounds. These compounds selectively inhibit parasite tubulin and arrest cells in mitosis.