Butenolides from Nectandra oppositifolia (Lauraceae) displayed anti-Trypanosoma cruzi activity via deregulation of mitochondria

Conserva, Geanne A. Alves; Costa-Silva, Thaís A.; Amaral, Maiara; Antar, Guilherme Medeiros; Neves, Bruno J.; Andrade, Carolina Horta; Tempone, André G.; Lago, João Henrique G.

doi:10.1016/j.phymed.2018.09.236

Cited by 17 publications

(13 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…13 C‐NMR spectrum showed peaks assigned to a γ‐lactone ring at δ 166.5 (C‐2), 127.2 (C‐3), 66.5 (C‐4), 157.6 (C‐5), 91.4 (C‐6), 150.2 (C‐1’), to a long side chain at δ 29.7–29.3 and to a terminal methyl group at δ 14.1 (C‐22’). The geometry of the alkylidene side chain was defined as E based on the 13 C‐NMR chemical shift observed for C‐1’ (δ 150.2), similar to those determined for related compounds 16,17‐dihydroisoobtusilactone (δ 150.2) [30] and isolinderanolide E (δ 150.2), [18] but different from the value described for miaolinolide (δ 151.3), [31] which exhibits Z geometry. The ESI‐HR‐MS spectrum of 6 showed the [M+H] + peak at m/z 421.3687 corresponding to the molecular formula C 27 H 48 O 3 , which indicated the presence of a saturated C 22 side chain.…”

Section: Resultsmentioning

confidence: 99%

“…In continuation of our studies concerning the discovery of new antiprotozoal compounds from Lauraceae species, [18,22,23] the phytochemical analysis from P. fulva leaves yielded three known γ‐lactones: majoranolide B ( 1 ), majorenolide ( 2 ) and majorynolide ( 3 ). Other two known compounds were isolated from the roots of P. americana : lincomolide D ( 4 ) and isolinderanolide E ( 5 ), as well as one new γ‐lactone named perseanolide (3 E ,4 R )‐3‐docosylidene‐4‐hydroxy‐5‐methylideneoxolan‐2‐one; ( 6 ).…”

Section: Introductionmentioning

confidence: 90%

“…Different γ‐lactones have been isolated from several genera of Lauraceae, such as Lindera , [8–10] Litsea , [11,12] Machilus , [13–15] Cinnamomum , [16,17] Nectandra , [18] and Persea [19,20] . Additionally, γ‐lactones isolated from Lauraceae species have been shown to possess diverse biological activities, such as antimycobacterial, [9] anti‐inflammatory [10] and cytotoxic activities [8,11,13,19,20] .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

γ‐Lactones from Persea americana and Persea fulva – in Vitro and in Silico Evaluation of Trypanosoma cruzi Activity

Reis

Umehara

Conceição

et al. 2021

Chemistry & Biodiversity

Self Cite

View full text Add to dashboard Cite

In the present study, five known γ‐lactones (majoranolide B – 1, majorenolide – 2, majorynolide – 3, lincomolide D – 4, and isolinderanolide E – 5), as well as a new one (perseanolide – 6), were isolated from Persea fulva and P. americana. All isolated compounds exhibited potential activity against trypomastigote forms of Trypanosoma cruzi, whereas compounds 2 (EC50 of 4.8 μM) and 6 (EC50 of 3.6 μM) displayed superior activity than the positive control benznidazole (EC50 of 16.4 μM), with selectivity index (SI) values of 17.8 and >55.6, respectively (benznidazole, SI>12.2). Molecular docking studies were performed for 1–6 against six T. cruzi molecular targets. Using this approach, we observed that, even though perseanolide (6) showed favorable docking to several studied targets, the results were especially promising for hypoxanthine phosphoribosyl transferase (PDB 1TC1). As PDB 1TC1 is associated to the transference of a monophosphorylated ribose from phosphoribosylpyrophosphate (PRPP) in the ribonucleotide synthesis pathway, this interaction may affect the survival of T. cruzi in mammalian cells. The data herein also indicate that possible intermolecular interactions between 6 and PDB 1TC1 derive from (i) hydrogen bonds in the α,β‐unsaturated‐γ‐lactone unity and (ii) hydrophobic interactions in the long‐chain alkyl group. Based on our results, perseanolide (6), reported for the first time in this work, can auspiciously contribute to future works regarding new trypanocidal agents.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

γ‐Lactones from Persea americana and Persea fulva – in Vitro and in Silico Evaluation of Trypanosoma cruzi Activity

Reis

Umehara

Conceição

et al. 2021

Chemistry & Biodiversity

Self Cite

View full text Add to dashboard Cite

show abstract

“…Particularly, isolinderanolide D ( 28 ) and isolinderanolide E ( 29 ) were isolated from Nectandra oppositifolia . These two compounds were effective against the trypomastigote and amastigotes forms of T. cruzi , without any mammalian cytotoxicity [ 82 ].…”

Section: Drug Targets and Inhibitorsmentioning

confidence: 99%

An Overview on Target-Based Drug Design against Kinetoplastid Protozoan Infections: Human African Trypanosomiasis, Chagas Disease and Leishmaniases

et al. 2021

View full text Add to dashboard Cite

The protozoan diseases Human African Trypanosomiasis (HAT), Chagas disease (CD), and leishmaniases span worldwide and therefore their impact is a universal concern. The present regimen against kinetoplastid protozoan infections is poor and insufficient. Target-based design expands the horizon of drug design and development and offers novel chemical entities and potential drug candidates to the therapeutic arsenal against the aforementioned neglected diseases. In this review, we report the most promising targets of the main kinetoplastid parasites, as well as their corresponding inhibitors. This overview is part of the Special Issue, entitled “Advances of Medicinal Chemistry against Kinetoplastid Protozoa (Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp.) Infections: Drug Design, Synthesis and Pharmacology”.

show abstract

“…Considering the urgent need for new treatments, natural products can be considered important sources to design potent and safer drug candidates [ 4 , 5 , 6 , 7 ]. Different studies [ 8 , 9 , 10 ] have shown that neolignans isolated from leaves and twigs of Nectandra leucantha (Lauraceae), as well as several related semi-synthetic derivatives, exhibited in vitro activity against T. cruzi [ 1 , 8 , 11 ]. In this work, molecular modeling techniques were employed to aid in the design of new neolignan-based compounds with improved biological activity against T. cruzi .…”

Section: Introductionmentioning

confidence: 99%

Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha

et al. 2021

Self Cite

View full text Add to dashboard Cite

In the present study, the phytochemical study of the n-hexane extract from flowers of Nectandra leucantha (Lauraceae) afforded six known neolignans (1–6) as well as one new metabolite (7), which were characterized by analysis of NMR, IR, UV, and ESI-HRMS data. The new compound 7 exhibited potent activity against the clinically relevant intracellular forms of T. cruzi (amastigotes), with an IC50 value of 4.3 μM and no observed mammalian cytotoxicity in fibroblasts (CC50 > 200 μM). Based on the results obtained and our previous antitrypanosomal data of 50 natural and semi-synthetic related neolignans, 2D and 3D molecular modeling techniques were employed to help the design of new neolignan-based compounds with higher activity. The results obtained from the models were important to understand the main structural features related to the biological response of the neolignans and to aid in the design of new neolignan-based compounds with better biological activity. Therefore, the results acquired from phytochemical, biological, and in silico studies showed that the integration of experimental and computational techniques consists of a powerful tool for the discovery of new prototypes for development of new drugs to treat CD.

show abstract

Butenolides from Nectandra oppositifolia (Lauraceae) displayed anti-Trypanosoma cruzi activity via deregulation of mitochondria

Cited by 17 publications

References 32 publications

γ‐Lactones from Persea americana and Persea fulva – in Vitro and in Silico Evaluation of Trypanosoma cruzi Activity

γ‐Lactones from Persea americana and Persea fulva – in Vitro and in Silico Evaluation of Trypanosoma cruzi Activity

An Overview on Target-Based Drug Design against Kinetoplastid Protozoan Infections: Human African Trypanosomiasis, Chagas Disease and Leishmaniases

Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha

Contact Info

Product

Resources

About