Licochalcone a Exhibits Leishmanicidal Activity in vitro and in Experimental Model of Leishmania (Leishmania) Infantum

Abstract

The efficacy of Licochalcone A (LicoA) and its two analogs were reported against Leishmania (Leishmania) amazonensis and Leishmania (Leishmania) infantum in vitro, and in experimental model of L. (L.) infantum in vitro. Initially, LicoA and its analogs were screened against promastigote forms of L. (L.) amazonensis. LicoA was the most active compound, with IC50 values of 20.26 and 3.88 μM at 24 and 48 h, respectively. Against amastigote forms, the IC50 value of LicoA was 36.84 μM at 48 h. In the next step, the effectivity of LicoA was evaluated in vitro against promastigote and amastigote forms of L. (L.) infantum. Results demonstrated that LicoA exhibited leishmanicidal activity in vitro against promastigote forms with IC50 values of 41.10 and 12.47 μM at 24 and 48 h, respectively; against amastigote forms the IC50 value was 29.58 μM at 48 h. Assessment of cytotoxicity demonstrated that LicoA exhibited moderate mammalian cytotoxicity against peritoneal murine macrophages; the CC50 value was 123.21 μM at 48 h and showed about 30% of hemolytic activity at concentration of 400 μM. L. (L.) infantum-infected hamsters and treated with LicoA at 50 mg/kg for eight consecutive days was able to significantly reduce the parasite burden in both liver and spleen in 43.67 and 39.81%, respectively, when compared with negative control group. These findings suggest that chalcone-type flavonoids can be a promising class of natural products to be considered in the search of new, safe, and effective compounds capable to treat canine visceral leishmaniosis (CVL).

Total Synthesis of the Natural Chalcone Lophirone E, Synthetic Studies toward Benzofuran and Indole-Based Analogues, and Investigation of Anti-Leishmanial Activity

“…Finally, the double bond proton signals at 8.01 and 7.96 ppm present J values (15.5 Hz) typical of the trans geometry. 13 C carbons (Figure 3B) have been assigned based on the spectral analysis reported in [25]. The 1 H and 13 C NMR spectra of the synthetic lophirone E (1) are reported in Figure 3A,B and they are in very good agreement with those reported in the literature [25].…”

“…13 C carbons (Figure 3B) have been assigned based on the spectral analysis reported in [25]. The 1 H and 13 C NMR spectra of the synthetic lophirone E (1) are reported in Figure 3A,B and they are in very good agreement with those reported in the literature [25]. In particular, the 2 -OH is clearly evident at 13.6 ppm, as well as the spin system of the B ring comprising proton signals at 8.19, 6.53 and 6.41 ppm (Figure 3A).…”

“…Moreover, selected chalcones are currently under clinical evaluation for the treatment of dermatological conditions [11]. In the field of tropical parasitic diseases, chalcones were reported as a promising new class of antileishmanial agents, showing selective activity in vitro and in vivo against different Leishmania species, and characterized by appropriate selectivity indexes [12,13]. The antileishmanial activity of chalcones has been largely investigated through phenotypic assays.…”

Quantum mechanical, molecular docking, molecular dynamics, ADMET and antiproliferative activity onTrypanosoma cruzi(Y strain) of chalcone (E)-1-(2-hydroxy-3,4,6-trimethoxyphenyl)-3-(3-nitrophenyl)prop-2-en-1-one derived from a natural product

“…71 Its therapeutic activity is, therefore, associated with control of the administered oral dose, since the estimated value of the lethal dose (LD 50 ) in rats between 300 and 2000 mg kg −1 suggests that the substance can be harmful by ingestion of a high oral dose. 72…”

Challenges and Tools for In Vitro Leishmania Exploratory Screening in the Drug Development Process: An Updated Review

“…Nevertheless, these models also reveal variation factors and potential biases, such as a low replication rate of amastigotes compared to promastigotes [32,33], the influence of the macrophage infection rate [34], and the variety of host cells used (primary cells or cell lines) [35]. Thus, although many studies show a correlation between the results obtained on in vitro promastigotes and (axenic) amastigotes [36][37][38][39][40][41], it seems important to take all these various factors and potential biases into account before implementing secondary screenings and interpreting them.…”