Search for Antimicrobial Activity Among Fifty-Two Natural and Synthetic Compounds Identifies Anthraquinone and Polyacetylene Classes That Inhibit Mycobacterium tuberculosis.

Drug-resistant tuberculosis threatens to undermine global control programs by limiting treatment options. New antimicrobial drugs are required, derived from new chemical classes. Natural products offer extensive chemical diversity and inspiration for synthetic chemistry. Here, we isolate, synthesize and test a library of 52 natural and synthetic compounds for activity against Mycobacterium tuberculosis. We identify seven compounds as antimycobacterial, including the natural products isobavachalcone and isoneorautenol, and a synthetic chromene. The plant-derived secondary metabolite damnacanthal was the most active compound with the lowest minimum inhibitory concentration of 13.07 µg/mL and a favorable selectivity index value. Three synthetic polyacetylene compounds demonstrated antimycobacterial activity, with the lowest MIC of 17.88 µg/mL. These results suggest new avenues for drug discovery, expanding antimicrobial compound chemistries to novel anthraquinone and polyacetylene scaffolds in the search for new drugs to treat drug-resistant bacterial diseases.

Synthesis of lupeol derivatives and their antileishmanial and antitrypanosomal activities.

The natural product lupeol 1 was isolated from aerial parts of Vernonia scorpioides with satisfactory yield, which made it viable to be used as starting material in semisynthetic approach. Ten lupeol derivatives 2-11 were prepared by classical procedures. Including, five new esters derivatives 7-11, which were obtained by structural modifications in the isopropylidene fragment. All semisynthetic compounds and lupeol 1-11 were confirmed by 1H NMR, 13C NMR and HRMS. Their antiprotozoal activity was evaluated in vitro against L. amazonensis and T. cruzi. Derivative 6 showed the best antitrypanosomal activity (IC50 = 12.48 µg/mL) and the lowest cytotoxic derivative (CC50 = 161.50 µg/mL). The mechanism of action of the most active derivatives (4, 6 and 11) is not dependent from the enzyme trypanothione reductase.

Multivariate SAR and QSAR of cucurbitacin derivatives as cytotoxic compounds in a human lung adenocarcinoma cell line.

This article describes structure-activity relationship (SAR/QSAR) studies on the cytotoxic activity in a human lung adenocarcinoma cell line (A549) of 43 cucurbitacin derivatives. Modeling was performed using the methods partial least squares with discriminant analysis (PLS-DA) and PLS. For both studies, the variables were selected using the ordered predictor selection (OPS) algorithm. The SAR study demonstrated that the presence or absence of cytotoxic activity of the cucurbitacins could be described using information derived from their chemical structures. The QSAR study displayed suitable internal and external predictivity, and the selected descriptors indicated that the observed activity might be related to electrophilic attack on cellular structures or genetic material. This study provides improves the understanding of the cytotoxic activity of cucurbitacins and could be used to propose new cytotoxic agents.