Synthesis, Antitubercular and Leishmanicidal Evaluation of Resveratrol Analogues

Abstract

In this paper we continue our efforts in the search for new Schiff bases as resveratrol analogues as promising antitubercular and antileishmanial agents. Compounds were evaluated in vitro against Mycobacterium tuberculosis and Leishmania species. Compounds showed varying activity against promastigotes of all Leishmania species tested (concentration leading to reduction of 50% of parasite growth-IC 50 values ranging from 1.60 to 15.53 µg mL ). Furthermore, the compounds showed comparable or better effect than drugs commonly used in tuberculosis treatment such as Cycloserine®. The analogue that was the most active for M. tuberculosis had minimal inhibitory concentration MIC 90 = 0.78 µg mL -1 . The in vitro cytotoxicity on Vero cells (CC 50 ), as well as the selectivity index (SI = CC 50 /MIC) were also evaluated, and showed that the synthesized analogues are not cytotoxic.

Resveratrol analogues present effective antileishmanial activity against promastigotes and amastigotes from distinct Leishmania species by multitarget action in the parasites

“…The antileishmanial effect of resveratrol and its analogues against different Leishmania species have been reported in the literature . However, in this study, we extended the investigation of effect of a new class of resveratrol analogues against promastigotes and intramacrophage amastigotes of different Leishmania species, aiming to evaluate their action against parasites able to cause TL and VL in the world.…”

Aza- and Azo-Stilbenes: Bio-Isosteric Analogs of Resveratrol

“…The replacement of one or both carbon atoms of the double bond between the mono-or poly-hydroxylated aromatic rings provides attractive biological properties to AZA-ST and AZO-ST such as antioxidant activities [51,64]. Some of them may be promising candidates to treat diseases whose current treatments are either non-existent or weakly efficient especially breast cancer with ERα negative [46,65,66], leishmaniasis and tuberculosis [62] and skin diseases [68]. Finally, the compounds of AZO-ST series 10 and 11 also show greater anti-fungal activities than hymexazol, a commercially available agricultural fungicide [67].…”

“…Other compounds of a new AZA-ST series 7 (Figure 9) bearing a hydroxyl group in the ortho position of cycle B were synthesized and have shown promising anti-leishmanicidal and antituberculosis activities [62]. The authors suggest that activity of compounds 7a-7f (which appear to be moderate) depends on the electronic density of the substituent in para position of cycle A.…”

Diarylethenes Display In Vitro Anti-TB Activity and Are Efficient Hits Targeting the Mycobacterium tuberculosis HU Protein

“…The 4′-hydroxydiarylethene 3 was less selective towards mycobacteria with an SI value of 4.4. Interestingly an aza-stilbene with the same substitution on the aromatic rings as 1 , showed an MIC value against the H37Rv strain of 6.9 µM and SI of 113 with reference to Vero cells [ 18 ]. This result is in agreement with our study, and it suggests that the chemical space of 2′-hydroxydiarylethenes is sufficiently selective for continuing efforts to optimize this hit against TB.…”