Synthesis of 1,2,3‐Triazole Derivatives of N , N ‐Dimethyltryptamine Isolated From Mimosa tenuiflora Root Bark: Antiplasmodial Activity In Silico and In Vitro
Renato Pinto de Sousa, William Cezar de Lima Silva, Caíque Lopes Duarte, Ana Claudia de Souza Pinto, Amanda Luisa Da Fonseca, Fernanda Alice De Oliveira, Fernando de Pilla Varotti, Bruno Antônio Marinho Sanchez, Mahendra Rai, Maurício Pires de Moura do Amaral, Mariana Helena Chaves, João Sammy Nery De Souza, Warley de Souza Borges, Gerardo Magela Vieira Júnior
Chemistry & Biodiversity October 1, 2026 DOI: 10.1002/cbdv.71849 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical in vitro and in silico study Peer reviewed |
|---|---|
| Population | W2 strain of Plasmodium falciparum parasites and TOV-21G cell line |
| Interventions | 1 2 |
| Measures | IC50, binding energy (kcal/mol) |
| Topics | 5-MeO-DMT DMT |
| Key points | Semisynthetic triazole derivatives of DMT were tested against P. falciparum W2; compound 4 was the most active (IC50 = 4.8 ± 0.32 µM) versus the parent compound (288.4 ± 28.53 µM) and showed higher selectivity toward the TOV-21G cell line. In silico, all derivatives showed more favorable binding energies than the parent, with compound 7 at −9.8 kcal/mol versus −6.9 kcal/mol for the crystallographic ligand. |
Abstract
ABSTRACT: Malaria is a severe parasitic disease, with Plasmodium falciparum as one of the main etiological agents. The growing resistance to antimalarial drugs underscores the urgent need for the development of new therapeutic agents. This study describes the semisynthesis of eight new 1,4‐disubstituted 1,2,3‐triazole derivatives ( 3–10 ) from N , N ‐dimethyltryptamine ( 1 ), isolated from Mimosa tenuiflora . The derivatives were obtained through copper(I)‐catalyzed alkyne–azide cycloaddition (CuAAC) reactions and characterized by NMR and mass spectrometry. Compound 1 showed low in vitro activity against the W2 strain of P. falciparum (IC 50 = 288.4 ± 28.53 µM), whereas compound 4 demonstrated promising activity (IC 50 = 4.8 ± 0.32 µM), with higher selectivity toward the TOV‐21G cell line. In in silico studies, all derivatives showed more favorable binding energy values compared to compound 1 , particularly compound 7 (−9.8 kcal/mol) relative to the crystallographic ligand (−6.9 kcal/mol). These results highlight the importance of structural modifications in the development of new antimalarial agents.
Comparable studies
Other preclinical and animal studies on DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The Hallucinogen N,N -Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator Mice and cell lines | 2009 | Experimental study | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Inhibitory effect of chlorpromazine on the syndrome of hyperactivity produced by l‐tryptophan or 5‐methoxy‐N,N‐dimethyltryptamine in rats treated with a monoamine oxidase inhibitor Rats | 1971 | Experimental study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study |