Synthesis and Bioactivity of Reduced Chalcones Containing Sulfonamide Side Chains

Abstract

The effect on the bioactivity of antibacterial sulfonamide drugs against malaria and tuberculosis via an increase of the lipid solubility groups by condensation with a reduced chalcone was investigated. Sulfonamide derivatives (8a-8d) were obtained via a 1,3-diarylpropane scaffold, prepared by reduction of the relevant chalcones, followed by the addition of a sulfonamide moiety via the Mannich and the Mannich exchange reactions. The ClogP values indicated that the lipophilicities of 8a-8d and intermediate reduced chalcones and N-alkylated reduced chalcones (5a-7a) were much higher than those of the sulfonamides (1a-1c). The N-alkylated reduced chalcone derivatives 6 and 7 exhibited the highest antimalarial (Plasmodium falciparum (NF54 strain)) activity. Addition of the sulfonamide group weakened the activity, even though some ClogP values were higher, while 1a-1c showed no activity. The reduced chalcones 5a and 5 showed potent growth inhibition of Mycobacterium tuberculosis (H37Rv strain), but the sulfonamide derivatives 8a and 8d showed no or insignificant activity (0 and 14%, respectively) against M. tuberculosis, despite high ClogP values. Thus, the possible increase in bioactivity expected from an increase in ClogP values (lipophilicity) might be counteracted by the higher molecular weight of the studied analogues.

Solvent‐Controlled Hydrogenation of 2’‐Hydroxychalcones: A Simple Solution to the Total Synthesis of Bussealins

“…[13] The use of more active Pd(OH) 2 catalyst in mixtures of organic solvents and water failed to improve the yields. [14] Better results were obtained when the catalytic hydrogenation was carried out under high hydrogen pressure. In this sense, the total reduction of chalcones was achieved on catalytic hydrogenation over Pd/C with hydrogen at 50 psi in mixtures of chloroform, water and acetic acid.…”

“…Thus, catalytic hydrogenation of chalcones over Pd/C in acetic acid yielded desired 1,3‐diarylpropanes, albeit in moderate yields [13] . The use of more active Pd(OH) 2 catalyst in mixtures of organic solvents and water failed to improve the yields [14] . Better results were obtained when the catalytic hydrogenation was carried out under high hydrogen pressure.…”

The 15th Frank Warren Organic Chemistry Conference

“…[20,21] The second by Prof. Susan Bonnet gave ab rief overview of her institution's6 0-year contribution to flavonoid chemistry movingo ntoh er group's current research into polymeric tannins as well as the biological activities of syntheticf lavonoid derivatives. [22,23] Prof. Rui Krause (Rhodes University) provided insight into mass spectrometry-guided metabolomics and its application to molecular social networking for the identification of newm arine natural products and elucidation of their biosynthetic pathways. [24] Dr.A nke Wilhelm (University of the Free State) divulged her recent resultsi nH PLC-based activity profiling in az ebrafish locomotivea ssay for the identification of GABA A receptor modulators ( Figure 3).…”

“…Natural Product Chemistry was the subject of two keynote lectures, the first by Prof. Wilfred Mabusela, who described his work relating to the phytochemical characterization of South African traditional medicinal plants . The second by Prof. Susan Bonnet gave a brief overview of her institution′s 60‐year contribution to flavonoid chemistry moving onto her group's current research into polymeric tannins as well as the biological activities of synthetic flavonoid derivatives . Prof. Rui Krause (Rhodes University) provided insight into mass spectrometry‐guided metabolomics and its application to molecular social networking for the identification of new marine natural products and elucidation of their biosynthetic pathways …”

Recent Highlights in Anti‐infective Medicinal Chemistry from South Africa

“…Accordingly, in this review, we discuss some recent highlights in medicinal chemistry research (2016–2020) in which researchers based in South Africa have made a significant contribution through medicinal chemistry methodology. Therefore, this review excludes recent contributions made in natural products chemistry . While substantial focus in South African medicinal chemistry is devoted to neurological disorders and cancer, this review will focus on those studies with promise against infectious diseases.…”