Evaluation of Antiproliferative and Antileishmanial Activities of R-(+)- limonene-derived 2-Amino-5-aryl-1,3,4-thiadiazoles

Abstract

Natural products are great prototypes for the development of new compounds with pharmacologic properties. In this work, the monoterpene R-(+)-limonene was used to obtain a series of 1,3,4-thiadiazoles and their antitumor and antileishmania activities against Leishmania amazonenses were investigated. The analogous 4-methyl (4b) was potentially active against melanoma tumor cells (UACC-62), while the derivative 4-methoxy (4c) and 4-dimethylamino (4d) were the most active against L. amazonensis.

Antiparasitic Behavior of Trifluoromethylated Pyrazole 2-Amino-1,3,4-thiadiazole Hybrids and Their Analogues: Synthesis and Structure-Activity Relationship

“…In general, the compounds of the series 3a-f were 1.4-fold most active compared to 2a-f, and the compounds 4a-f were 1.2-fold most active than 2a-f. Comparing the works of Batista (Batista et al, 2019) and Vandresen (Vandresen et al, 2017), the transformation of the thiosemicarbazone group into 2-amino-1,3,4-thiadiazole derivative led to compounds in the range 1.4 to 6-fold less actives.…”

“…Also, the sulfur atom in this heterocycle imparts improved liposolubility. More specifically, 2-amino-1,3,4thiadiazole series (Jain et al, 2013;Martins et al, 2016;Vandresen et al, 2017;Serban, 2019;Freitas et al, 2020) and their thiosemicarbazone analogue (De Melos et al, 2015;Batista et al, 2019) have been studied for potential antileishmanial and trypanocidal activity ( Figures 1C-E). Comparing the results reported for compounds IV and V, the 2-amino-1,3,4-thiadiazole derivatives were less active than the thiosemicarbazone derivatives ( Figures 1C, D).…”

Antiproliferative Activity and Ultrastructural Changes in Promastigote and Amastigote forms of Leishmania amazonensis Caused by Limonene‐Acylthiosemicarbazide Hybrids

“…In this regard, the antiprotozoal activity for both enantiomers were confirmed by in vitro and in vivo assays against promastigote and amastigote forms of L. amazonensis. [35][36][37][38] Thus, the objective of this work was the development and synthesis of a new series of limonene-acylthiosemicarbazide hybrids compounds that has antiproliferative activity against L. amazonensis and low cytotoxicity to mammalian cells.…”