Novel prenyloxy chalcones as potential leishmanicidal and trypanocidal agents: Design, synthesis and evaluation

Espinoza‐Hicks, José C.; Chacón-Vargas, Karla Fabiola; Hernández-Rivera, J. L.; Nogueda‐Torres, Benjamín; Tamariz, Joaquı́n; Sánchez-Torres, Luvia Enid; Camacho‐Dávila, Alejandro A.

doi:10.1016/j.ejmech.2019.02.028

Cited by 25 publications

(15 citation statements)

References 31 publications

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“…The analogs were synthesized and constitute structures similar to the natural products LicoA (1) and also Echinatin (2) (Figure 1). The analog LLA1 (1a) (Figure 2) is a derivate of LicoA that belongs to the class of chalcones containing the group O-prenil (17). In another study, the evaluation of a series of prenyloxy and geranyloxy chalcones against Leishmania (Leishmania) mexicana and Trypanosoma cruzi demonstrated that the position of the substituent has an influence on the activity and selectivity of these compounds (18).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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).

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Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…Some natural products such as acetophenones and chalcones, as well as chromane-type substances, such as chromones and flavones, exhibit trypanocide activity [ 4 , 5 , 6 , 7 , 8 ]. In these compounds, besides the phenolic hydroxyls are also frequently present one or several free or cyclized isoprenyl units.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of Trypanocidal Activity of Chromane-Type Compounds and Acetophenones

et al. 2021

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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.

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“…They are considered as one of the privileged scaffolds displaying multifarious applications in a wide variety of scientific domains, such as anticancer, 17,18 anti-inflammatory, 19 antioxidant, 20 antimicrobial, anti-tubercular, 21 anti-HIV, 22 antimalarial, 23 anti-allergic, 24 and leishmanicidal activities. 25 Notably, different mechanisms of action have been described for chalcones, including the induction of apoptosis, inhibition of cell proliferation, inhibition of angiogenesis, blockade of nuclear factor-kappa B (NF-κB) signaling pathway and reversal of multidrug resistance or a combination of these mechanisms. 26,27 Furthermore, chalcones are powerful tubulin assembly inhibitors, with almost similar potency to CA-4.…”

Section: Introductionmentioning

confidence: 99%

<p>Novel HDAC/Tubulin Dual Inhibitor: Design, Synthesis and Docking Studies of α-Phthalimido-Chalcone Hybrids as Potential Anticancer Agents with Apoptosis-Inducing Activity</p>

Mourad

Jones³

2020

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Introduction: In order to develop novel anticancer HDAC/tubulin dual inhibitors, a novel series of α-phthalimido-substituted chalcones-based hybrids was synthesized and characterized by IR, 1 H NMR, 13 C NMR, mass spectroscopy and X-ray analysis. Methods: All the synthesized compounds were evaluated for their in vitro anticancer activity against MCF-7 and HepG2 human cancer cell lines using MTT assay. To explore the mechanism of action of the synthesized compounds, in vitro β-tubulin polymerization and HDAC 1 and 2 inhibitory activity were measured for the most potent anticancer hybrids. Further, cell cycle analysis was also evaluated. Results: The trimethoxy derivative 7j showed the most potent anticancer activity, possessed the most potent β-tubulin polymerase and HDAC 1 and 2 inhibitory activity and efficiently induced cell cycle arrest at both G2/M and preG1phases in the MCF-7 cell line. Keywords: chalcones, α-phthalimido, anticancer, cell cycle, histone deacetylase inhibitor, tubulin polymerase inhibitor-Cell cycle analysis was done for the most active compounds and it was clear that the tested compounds successfully arrested cell cycle at G2/M phase and induced preG1 apoptosis compared to the reference compounds.-Molecular docking studies were carried out to explore the binding pattern of the most active synthesized compounds toward colchicine binding site in tubulin protein and HDAC2 active site.

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Novel prenyloxy chalcones as potential leishmanicidal and trypanocidal agents: Design, synthesis and evaluation

Cited by 25 publications

References 31 publications

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

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

Synthesis and Evaluation of Trypanocidal Activity of Chromane-Type Compounds and Acetophenones

<p>Novel HDAC/Tubulin Dual Inhibitor: Design, Synthesis and Docking Studies of α-Phthalimido-Chalcone Hybrids as Potential Anticancer Agents with Apoptosis-Inducing Activity</p>

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