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Eleven indanoyl derivatives were synthesized and, along with methyl jasmonate, evaluated as isoflavonoid-phytoalexin elicitors in two cultivars of common bean ( Phaseolus vulgaris L. cvs. ICA-Cerinza and Uribe Rosado, tolerant and susceptible to anthracnose, respectively). Indanoyl derivatives (an ester, two amides, and eight indanoyl-amino acid conjugates) were obtained from 1-oxo-indane-4-carboxylic acid. In general, the accumulation of isoflavonoid-type phytoalexins, such as isoflavones (genistein, daidzein, and 2'-hydroxygenistein), isoflavanones (dalbergioidin and kievitone), isoflavan (phaseollinisoflavan), coumestrol, and pterocarpans (phaseollidin and phaseollin), was dependent on the common bean cultivar, the post-induction time, and the elicitor structure. Isoflavones, dalbergioidin, and coumestrol reached their highest amounts during the first 48 to 72 h, whereas kievitone, phaseollinisoflavano, and the pterocarpans reached maximum levels between 72 and 96 h. The 1-oxo-indanoyl-L-isoleucine methyl ester elicited the highest levels of phytoalexins (similar to those elicited by the methyl jasmonate) and showed no significant phytotoxic effects on common bean seedlings. The indanoyl-type synthetic elicitor, 1-oxo-indanoyl-L-isoleucine methyl ester, may represent a promising agronomic alternative for disease control in common bean by enhancing the accumulation of antimicrobial isoflavonoid phytoalexins.

American trypanosomiasis (Chagas disease) caused by the Trypanosoma cruzi parasite, is a severe health problem in different regions of Latin America and is currently reported to be spreading to Europe, North America, Japan, and Australia, due to the migration of populations from South and Central America. At present, there is no vaccine available and chemotherapeutic options are reduced to nifurtimox and benznidazole. Therefore, the discovery of new molecules is urgently needed to initiate the drug development process. Some acetophenones and chalcones, as well as chromane-type substances, such as chromones and flavones, are natural products that have been studied as trypanocides, but the relationships between structure and activity are not yet fully understood. In this work, 26 compounds were synthesized to determine the effect of hydroxyl and isoprenyl substituents on trypanocide activity. One of the compounds showed interesting activity against a resistant strain of T. cruzi , with a half effective concentration of 18.3 µM ± 1.1 and an index of selectivity > 10.9.

In continuation of our efforts to identify promising antileishmanial agents based on the chroman scaffold, we synthesized several substituted 2H -thiochroman derivatives, including thiochromenes, thichromanones and hydrazones substituted in C-2 or C-3 with carbonyl or carboxyl groups. Thirty-two compounds were thus obtained, characterized, and evaluated against intracellular amastigotes of Leishmania ( V ) panamensis . Twelve compounds were active, with EC 50 values lower than 40 µM, but only four compounds displayed the highest antileishmanial activity, with EC 50 values below 10 µM; these all compounds possess a good Selectivity Index > 2.6. Although two active compounds were thiochromenes, a clear structure-activity relationship was not detected since each active compound has a different substitution pattern., Competing Interests: The authors declare no conflict of interest.

Cutaneous leishmaniasis (CL) is a neglected tropical disease, which causes severe skin lesions. Due to the lack of effective vaccines, and toxicity or reduced effectiveness of available drugs in addition to complex and prolonged treatments, there is an urgent need to develop alternatives for the treatment for CL with different mechanisms of action. In our effort to search for new promising hits against Leishmania parasites we prepared 18 acyl hydrazone derivatives of thiochroman-4-ones. Compounds were evaluated for their in vitro antileishmanial activity against the intracellular amastigote form of Leishmania panamensis and cytotoxic activity against human monocytes (U-937 ATCC CRL-1593.2). Our results show that derivatization of the thiochroman-4-ones with acyl hydrazones significantly enhances the antileishmanial activity. Among the compounds tested semicarbazone and thiosemicarbazone derivatives of thioflavanone 19 and 20 displayed the highest antileishmanial activities, with EC 50 values of 5.4 and 5.1 µM and low cytotoxicities (100.2 and 50.1 µM respectively), resulting in higher indexes of selectivity (IS)., Competing Interests: The authors declare no conflict of interest.

The S-containing heterocyclic compounds benzothiopyrans or thiochromones stand out as having promising biological activities due to their structural relationship with chromones (benzopyrans), which are widely known as privileged scaffolds in medicinal chemistry. In this work, we report the synthesis of 35 thiochromone derivatives and the in vitro antileishmanial and cytotoxic activities. Compounds were tested against intracellular amastigotes of Leishmania panamensis and cytotoxic activity against human monocytes (U-937 ATCC CRL-1593.2). Compounds bearing a vinyl sulfone moiety, 4h , 4i , 4j , 4k , 4l and 4m , displayed the highest antileishmanial activity, with EC 50 values lower than 10 μM and an index of selectivity over 100 for compounds 4j and 4l . When the double bond or the sulfone moiety was removed, the activity decreased. Our results show that thiochromones bearing a vinyl sulfone moiety are endowed with high antileishmanial activity and low cytotoxicity., Competing Interests: The authors declare no conflicts of interest.

Six derivatives of the known biopesticide rotenone were prepared by several chemical transformations. Rotenone and its derivatives showed differential in vitro antiparasitic activity and selective cytotoxicity. In general, compounds were more active against Plasmodium falciparum than Leishmania panamensis. Rotenone had an EC50 of 19.0 µM against P. falciparum, and 127.2 µM against L. panamensis. Although chemical transformation does not improve its biological profile against P. falciparum, three of its derivatives showed a significant level of action within an adequate range of activity with EC50 values < 50.0 µM. This antiplasmodial activity was not due to red blood cell hemolysis, since LC50 was >>400 µM. On the other hand, all derivatives displayed a non-specific cytotoxicity on several cell lines and primary human cell cultures.

In the present work, isoflavonoid phytoalexin production in response to the application of salicylic acid in cotyledons of four common bean (Phaseolus vulgaris) cultivars (SA) was evaluated. The time-course and dose-response profiles of the induction process were established by quantifying the isoflavonoids by HPLC. Cotyledons of anthracnose-resistant cultivars induced by SA produced substantially higher phytoalexin contents as compared to the susceptible ones. In addition, maximum levels of phytoalexins (50-100 fold increases) were reached between 96 and 144 h, and when a concentration of SA from 3.62 to 14.50 mM was used. The observations also indicate that there was a relatively good correlation between the phytoalexin contents and the inhibitory effect against C. lindemuthianum; the higher antifungal activity was observed during the first 48 hours for extracts from cotyledons treated with SA at 1.45 and 3.62 mM, and between 96 and 144 h after induction. Finally, compounds structurally related to SA (dihydro-quinazolinones and some imines) showed a strong elicitor effect. Moreover, induced extracts from cotyledons treated with these potential elicitors, besides the properly elicitors, displayed a weak to moderated antifungal activity. These compounds may be considered good candidates for developing of new phytoprotectants. Furthermore, phytoalexin-eliciting substances may contribute for selecting disease resistant cultivars.

Several aliphatic and aromatic lactones and two dimers were synthesized using the sequence: allylation - esterification - metathesis. These compounds were active in vitro against intracellular amastigotes of Leishmania panamensis. The structure-activity relationship showed the importance of the aliphatic side chain to enhance the biological activity and to obtain lower cytotoxicity. It was also observed that a decrease in the size of the lactone ring increases the selectivity index.

Ground pearl (Eurhizococcus colombianus) is a crop pest in Colombia, with special impact on fig, grass, rubus and tomato plants. The insect is resistant to external insecticide application because it produces a thick waxy shell that isolates it from the environment. The composition of this shell was determined by NMR and MS as a triglyceride, whose fatty acid is transformed into other products with the metamorphosis of the insect. Additionally, several enzymatic inhibitors were assayed to control the insect with negative results.

Several natural and hemisyntetic passifloricins were assayed against Leishmania panamensis amastigotes. High leishmanicidal activity as well as toxicity was observed. The structure of a new compound is also reported.