Synthesis of 1,2,3‐Triazole Derivatives of N , N ‐Dimethyltryptamine Isolated From Mimosa tenuiflora Root Bar
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 JúniorABSTRACT
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.