Indoquinoline Alkaloids from Sida rhombifolia (L.) (Malvaceae) and Antimicrobial Evaluation of Cryptolepinone Derivatives

Abstract

Considering the relevance of natural products to the development of new drugs, this study focuses on the species Sida rhombifolia (L.), Malvaceae, widely used as a traditional remedy in several countries. The species is used to treat several diseases such as fevers, skin diseases, stomach pain, diarrhea, gum infection, conjunctivitis, urinary infections and inflammation. Many researchers around the word have investigated its pharmacological potential, and many uses have been confirmed. In spite of that, the phytochemical composition of its extracts is still poorly investigated. This research aims to make advances on the understanding of the constituents of S. rhombifolia identifying its alkaloidal compounds using ultra-high performance liquid chromatography coupled to mass spectrometry (UPLC-QTOF-MS/MS). By analyzing its alkaloidal fraction it was possible to identify: 11-cryptolepine carboxylic acid (1), cryptolepine (2), quindoline (3), 11-methoxyquidoline (4), quindolinone (5), cryptolepinone (6), and 11-quindoline methyl ester (7). The alkaloids 1 and 7 are being reported for the first time from Sida genus. Based on the antimicrobial potential of cryptolepinone-type alkaloids, we prepared by semi-synthesis two cryptolepinone derivatives: 10-methylcryptolepinone (8) and the unreported compound 10-ethylcryptolepinone (9). Both derivatives were tested against fungae and bacterial strains and 10-methylcryptolepinone (8) showed strong activity against Cryptococcus neoformans, Candida albicans, C. tropicalis, Aspergillus fumigatus and A. flavus.