15 beta-Senecioyl-oxy-ent-kaur-16-en-19-oic Acid, a Diterpene Isolated from Baccharis lateralis, as Promising Oral Compound for the Treatment of Schistosomiasis

Author(s)

Sessa, Deborah P. ^[1] ; Mengarda, Ana C. ^[2] ; Simplicio, Paula E. ^[2] ; Antar, Guilherme M. ^[3] ; Lago, Joao Henrique G. ^[1] ; de Moraes, Josue ^[2]

Affiliation

^[1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210180 Santo Andre, SP - Brazil

^[2] Univ Guarulhos, Nucleo Pesquisa Doencas Negligenciadas, BR-07023070 Guarulhos, SP - Brazil

^[3] Univ Sao Paulo, Inst Biociencias, Dept Bot, BR-05508090 Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of Natural Products; v. 83, n. 12, p. 3744-3750, DEC 24 2020.
• Web of Science Citations: 5

Abstract

Praziquantel is the only available drug to treat schistosomiasis, and therefore, urgent studies must be performed to identify new anthelmintic agents. This study reports the anthelmintic evaluation of two related ent-kaurane diterpenes isolated from aerial parts of Baccharis lateralis (Asteraceae), entkaur-16-en-19-oic acid (1) and 15 beta-senecioyl-oxy-ent-kaur-16-en-19oic acid (2) against Schistosoma mansoni in vitro and in a murine model of schistosomiasis. Both compounds exhibited in vitro activity with lethal concentration 50% (LC50) values of 26.1 mu M (1) and 11.6 mu M (2) as well as reduced toxicity against human cell lines, revealing a good selectivity profile, mainly with compound 2 (selectivity index > 10). Compound 2 also decreased egg production and caused morphological alterations in the parasite reproductive system. In mice infected with S. mansoni, oral treatment with compound 2 at 400 mg/kg, the standard dose used in this model of schistosomiasis, caused a significant reduction in a total worm burden of 61.9% (P < 0.01). S. mansoni egg production, a key mechanism for both transmission and pathogenesis, was also markedly reduced. In addition, compound 2 achieved a significant reduction in hepatosplenomegaly. Therefore, the diterpene 15 beta-senecioyl-oxy-ent-kaur-16-en-19-oic acid (2) has an acceptable cytotoxicity profile and is orally active in a murine schistosomiasis model. (AU)

• FAPESP's process: 16/22488-3 - Drug repositioning for neglected diseases: identification of novel anthelmintic agents
• Grantee: Josué de Moraes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/07885-1 - Biomolecules from plant species of remnant areas of the Atlantic Forest and Cerrado to treat neglected tropical diseases - chemical and pharmacological aspects
• Grantee: João Henrique Ghilardi Lago
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants