Antimalarial Alkoxylated and Hydroxylated Chalones:  Structure−Activity Relationship Analysis

Abstract

Chalcones with 2',3',4'-trimethoxy, 2',4'-dimethoxy, 4'-methoxy, 4'-ethoxy, 2',4'-dihydroxy, and 4'-hydroxy groups on ring B were synthesized and evaluated in vitro against Plasmodium falciparum (K1) in a [3H] hypoxanthine uptake assay. The other ring A was quinoline, pyridine, naphthalene, or phenyl rings with electron-donating or electron-withdrawing substituents of varying lipophilicities. Trimethoxy 6 and 27, dimethoxy 7, 8, 29, and methoxy 31 analogues had good in vitro activities (IC(50) < 5 microM). 3-Quinolinyl ring A derivatives were well represented among the active compounds. Hydroxylated chalcones were less active than the corresponding alkoxylated analogues. When evaluated in vivo, 8 and 208 were comparable to chloroquine in extending the lifespan of infected mice. Multivariate data analysis showed that in vitro activity was mainly determined by the properties of ring B. Quantitative structure-activity relationship models with satisfactory predictive ability were obtained for various B ring chalcones using projections to latent structures. A model with good predictability was proposed for 19 active chalcones. Size and hydrophobicity were identified as critical parameters.

Synthesis, Characterization of Biologically Potent Novel Chalcones Bearing Urea, Thiourea and Acetamide Linkages

“…These facts further emphasize the imperative necessity to find new effectual and secure compounds to maintain and improve the management and prevention of opportunistic microbial and tubercular infections in an innovative era of exhaustive infectious disease control, elimination, and eradication. Chalcones comprise an important class of natural products belonging to the flavonoid family, which exhibit motivating biological activities together with anti-inflammatory [1], anti bacterial [2], anti oxidant [3], anti malarial [4] and anti cancer [5]. Due to their abundance in plants and ease of synthesis, this class of compounds has generated great interest for possible therapeutic uses.…”

Synthesis of Biologically Active Chalcon Analogues via Claisen-Schmidt Condensation in Solvent-Free Conditions: Supported Mixed Addenda Heteropoly Acid as a Heterogeneous Catalyst

“…Chalcones belonging to flavonoid family have displayed a broad spectrum of biological activities, among which antimalarial 1 , anticancer 2 , antimitotic 3 , antibacterial 4 , antiADIS 5 , antihyperglycemic 6 activities have been reported. These compounds are of high interest due to their use as a key precursor in the synthesis of many biological important heterocycles such as benzothiazepine 7 , pyrazolines 8 and flavones 9 .…”

Assessment of Substituent Effects and Antimicrobial Activities of some 2ʹ,5ʹ-Dimethyl Phenyl Chalcones

“…Compounds with the backbone of chalcone possesses various biological activities such as anti-microbial [7], anti-inflammatory [8], analgesic [9], anti-ulcerative [10], immunemodulatory [11], anti-malarial [12], anti-cancer [13], anti-viral [14], anti-leishmanial [15], anti-oxidant [16], anti-tubercular [17], anti-hyperglycemic [18] etc. A compound having anti-oxidant activity prevents and counteracts the damage of the human tissue by the normal effects of physiological oxidation [19].…”