Synthesis, Structure–Activity Relationships, and Biological Studies of Chromenochalcones as Potential Antileishmanial Agents

Abstract

Antileishmanial activities of a library of synthetic chalcone analogues have been examined. Among them, five compounds (11, 14, 16, 17, 22, and 24) exhibited better activity than the marketed drug miltefosine in in vitro studies against the intracellular amastigotes form of Leishmania donovani. Three promising compounds, 16, 17, and 22, were tested in a L. donovani/hamster model. Oral administration of chalcone 16, at a concentration of 100 mg/kg of body weight per day for 5 consecutive days, resulted in >84% parasite inhibition at day 7 post-treatment and it retained the activity until day 28. The molecular and immunological studies revealed that compound 16 has a dual nature to act as a direct parasite killing agent and as a host immunostimulant. Pharmacokinetics and serum albumin binding studies also suggest that compound 16 has the potential to be a candidate for the treatment of the nonhealing form of leishmaniasis.

Cell death and ultrastructural alterations in Leishmania amazonensis caused by new compound 4-Nitrobenzaldehyde thiosemicarbazone derived from S-limonene

“…These observations may indicate parasite death caused by apoptosis. Shivahare et al (2014) [ 35 ] showed that a chromenochalcone exhibited leishmanicidal effects against Leishmania donovani by causing loss in membrane potential and phosphatidylserine exposure, thus exerting cell death via apoptosis in treated promastigotes.…”

Evaluation of antimicrobial, antibiofilm and carbonic anhydrase inhibition profiles of 1,3‐bis‐chalcone derivatives

“…The chalcones, that have this structural feature, are among the important compounds that we frequently encounter in the literature in terms of both their useful synthetic properties and biological activity they exhibit . They have a broad spectrum of biological activity such as antimicrobial, antifungal, anticancer, anti‐inflammatory, analgesic, antioxidant, antileishmanial and antimalarial activities. In addition, many heterocyclic and polyfunctional compounds such as pyrazole, pyrimidine, pyridine, pyridone, quinoline and isoxazole derivatives can be synthesized easily starting from chalcones.…”

In Vitro Antimalarial Evaluation of Piperidine- and Piperazine-Based Chalcones: Inhibition of Falcipain-2 and Plasmepsin II Hemoglobinases Activities from Plasmodium falciparum

“…Chalcones or 1,3‐diaryl‐2‐propen‐1‐ones (Figure ) belonging to the flavonoid family are natural products with wide spread distribution in fruits, vegetables, spices and tea. Recently, the compounds with chalcone (1,3‐diaryl‐2‐propen‐1‐one) backbone have been reported to exhibit diverse biological properties, including antimalarial, antiviral, antibacterial, antituberculosis, antifungal, anticancer, antileishmaninal, antigiardial and antiinflammatory . A number of chalcone derivatives have also been found to inhibit several important enzymes in cellular systems, including protein tyrosine kinase, malarial aspartic protease (PM II) and malarial cysteine protease (FP‐1) .…”