Larvicidal activity of substituted chalcones against Aedes aegypti (Diptera: Culicidae) and non-target organisms.

BACKGROUND: The expansion of Aedes aegypti (Diptera: Culicidae) population has increased the number of cases of arboviruses, in part due to the inefficiency and toxicity of the chemical control methods available to control this vector. We synthesized 19 chalcone derivatives and examined their activity against Ae. aegypti larvae in order to select larvicidal compounds that are non-toxic to other organisms. RESULTS: Seven chalcone derivatives (3a, 3e, 3f, 6a, 6c, 6d, and 6f) had lethal concentrations of substituted chalcones capable of killing 50% (LC50 ) values lower than 100 mg mL-1 at 24 h post-treatment, which is the dose that the World Health Organization recommends for the selection of promising larvicides. The type of substituent added to (E)-1,3-diphenylprop-2-en-1-one (3a) markedly affected the larvicidal activity. Addition of chlorine, bromine and methoxy groups to the aromatic rings reduced the larvicidal activity, while replacement of the B-ring (phenyl) by a furan ring significantly increased the larvicidal activity. The furan-chalcone (E)-3-(4-bromophenyl)-1-(furan-2-yl)prop-2-en-1-one (6c) killed Ae. aegypti larvae (LC50 = 6.66 mg mL-1 ; LC90 = 9.97 mg mL-1 ) more effectively than the non-substituted chalcone (3a) (LC50 = 14.43 mg mL-1 ; LC90 = 20.96 mg mL-1 ), and was not toxic to the insect Galleria mellonella, to the protozoan Tetrahymena pyriformis, and to the algae Chorella vulgaris. CONCLUSIONS: The substitution pattern of chalcones influenced their larvicidal activity. In the set of compounds tested, (E)-3-(4-bromophenyl)-1-(furan-2-yl)prop-2-en-1-one (6c) was the most effective larvicide against Ae. aegypti, with no clear signs of toxicity to other animal models. Its mechanism of action and effectiveness under field conditions remain to be determined.

Structure-activity relationship of natural and synthetic coumarin derivatives against Mycobacterium tuberculosis.

Aim: Eight coumarin derivatives (1a-h) obtained from natural (-)-mammea A/BB (1) and 13 synthetic coumarins (2-14) had their cytotoxicity and biological activity evaluated against Mycobacterium tuberculosis H37Rv reference strain and multidrug-resistant clinical isolates. Materials & methods: Anti-M. tuberculosis activity was evaluated by resazurin microtiter assay plate, and the cytotoxicity of natural and synthetic products using J774A.1 macrophages by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Results: Compounds 1g, 5, 6, 12 and 14 were more active against M. tuberculosis H37Rv and multidrug-resistant clinical isolates with MIC values ranging from 15.6 to 62.5 µg/ml. Conclusion: These results demonstrate that the coumarin derivatives were active against multidrug-resistant clinical isolates, becoming potential candidates to be used in the treatment of resistant tuberculosis.