Antimalarial Quinones for Prophylaxis Based on a Rationale of Inhibition of Electron Transfer in Plasmodium

Abstract

Knowledge of the biochemistry of Plasmodium is emerging as a new field. Previous studies showed that the parasite apparently requires electron transfer for energy, and techniques to study such energy mechanisms are available.

The anti-cancer, anti-inflammatory and tuberculostatic activities of a series of 6,7-substituted-5,8-quinolinequinones

“…Generally, the quinolinequinones containing a halogen at the 6-and/or 7-position exhibited slightly better tuberculostatic activity than derivatives containing a thiol group at the 6-or 7-position (compare entries 1-12 with [13][14][15][16][17][18][19]; however the precise levels of activity depended on the substitution pattern. Previous studies have revealed that chloro-ethylaminoquinolinequinones, such as 8c (entry 9), and the subsequent tricyclic compound 22 (entry 18) exhibited promise as TB-drugs.…”

“…The compounds have been broadly grouped into those containing two halogen substituents (entries 1 and 2), an amine and halogen functionality (entries 3-12), those with a mono-sulfur functionality (entries [13][14][15][16][17][18][19][20][21][22][23][24], and the di-sulfur containing derivatives (entries 25-28).…”

“…13,14 Other biologically active 5,8-quinolinequinones include the potent anti-inflammatory agents Ascidiathiazones A (2) and B (3), recently isolated from the New Zealand ascidian Aplidium sp., 15 the antituberculostatic thiazole-containing quinolinequinones, such as 4, 16,17 and 7-heptadecylsulfanyl-6-hydroxy-5,8-quinolinequinone (5), which exhibited promising anti-malarial activity. 18,19 Given the potential of quinolinequinones in the treatment of a variety of diseases and, in particular, the potential of less complex quinolinequinones (e.g., 5) to have interesting biological activities, we synthesised and tested a number of 6,7-substituted-5,8-quinolinequinones for their anti-proliferative, anti-inflammatory, and tuberculostatic activities. Few 6,7-substituted-5,8-quinolinequinones have been screened in multiple assays and given the broad biological profiles of quinolinequinones, this makes it difficult to determine the drug's specificity.…”

“…Few 6,7-substituted-5,8-quinolinequinones have been screened in multiple assays and given the broad biological profiles of quinolinequinones, this makes it difficult to determine the drug's specificity. Moreover, relatively few bicyclic thiol-substituted quinolinequinones have been synthesised 12,[16][17][18][20][21][22][23][24][25][26][27][28] and the subsequent biological studies performed on these compounds have primarily focussed on the role of mono-or di-thio-quinolinequinones as anti-malarial 18,19,29 and anti-fungal [24][25][26] agents. A comparison of the activities of a variety of 6,7-substituted-5,8-quinolinequinones in a number of different assays provides valuable information on how the substitution pattern affects biological activity and will highlight key factors important for the development of better and more 0968-0896/$ -see front matter Ó 2010 Elsevier Ltd. All rights reserved.…”

Discovery of Novel Synthetic Methodologies and Reagents during Natural Product Synthesis in the Post-Palytoxin Era

“…Several quinolines isolated from natural sources or derivatives thereof are significant with respect to their use as antimalarials. 226 Chloroquine (203) and hydroxychloroquine (204) are among the most famous antimalarials containing the quinoline scaffold and have additionally been used to suppress the disease process in rheumatoid arthritis. As a result of their important biological activities, the development of novel strategies to access substituted quinolines has been an important focus of synthetic method development.…”