Exploration of a New Type of Antimalarial Compounds Based on Febrifugine

Abstract

Febrifugine (1), a quinazoline alkaloid, isolated from Dichroa febrifuga roots, shows powerful antimalarial activity against Plasmodium falciparum. The use of 1 as an antimalarial drug has been precluded because of side effects, such as diarrhea, vomiting, and liver toxicity. However, the potent antimalarial activity of 1 has stimulated medicinal chemists to pursue compounds derived from 1, which may be valuable leads for novel drugs. In this study, we synthesized a new series of febrifugine derivatives formed by structural modifications at (i) the quinazoline ring, (ii) the linker, or (iii) the piperidine ring. Then, we evaluated their antimalarial activities. Thienopyrimidine analogue 15 exhibited a potent antimalarial activity and a high therapeutic selectivity both in vitro and in vivo, suggesting that 15 is a good antimalarial candidate.

Synthesis and Antibacterial Activity of Thienopyrimidine Amide Derivatives

“…This scaffold shows a broad spectrum of biological activities. The thienopyrimidines were assessed as antitumour [6][7][8][9], medicine [10], enzyme [11][12][13][14], phosphodiesterase inhibitors [15], antioxidative [16,17], antimalarial drug [18,19], antibacterial drug [20], antiviral [21], antifungal [22,23], medication [24], antiplatelet [25] and medicament [26]. In view of these observations, the varied biological property of thienopyrimidine pharmacophore impelled to synthesize the title compounds.…”

Design, docking analysis, identification, and synthesis of novel 3-(((substituted phenyl) amino)methyl)-2-methylquinazolin-4(3<i>H</i>)-one compounds to fight tuberculosis

“…Quinazolin-4(3H)-one and related quinazolines are classes of fused heterocycles that are of considerable interest because of the diverse range of their biological properties. Quinazolin-4(3H)-one with a substituted group at position 3 has diverse therapeutic activities including antibacterial (7), antifungal (8), antimalarial (9), anticancer (10), antiinflammatory (11), anticonvulsant (12), and analgesic (13) activity. Quinazoline and its derivatives with a different pharmacophore group each have different modes of action in the treatment of TB.…”

Zn[(L)-proline] as a Recyclable and Green Catalyst for Efficient and One-pot Three-Component Synthesis of 1,4-Dihydro- pyridines Under Solvent-Free and Microwave Irradiation Conditions

“…Other synthetic methods includes treatment of phosphoranes with NaH/CH 3 CN 20 , pyrolysis of Schiff bases derived from 3-amino-1,2,3-triazineone in paraffin oil at 300 0 C 21 . The most general method for synthesis of these compounds involves cyclocondensation of anthranilamides with aldehydes in the presence of various promoting agents, such as p-toluenesulfonic acid/DDQ 22 , I 2 /KI in water 23 , CuCl 2 in ethanol 24 , DDQ/DMF 25 , Sc(oTf) 3 26 , NaHSO 3 27 , SnCl 4 In continuation of our interest in finding environmentally benign method for the synthesis of various heterocyclic compounds [37][38][39][40][41][42] , here in we want to report for first time, a new and efficient synthesis of 4(3H)-quinazolinones in the presence ofZn[(L)-proline] 2 as a lewis acid catalyst under solvent-free conditions (Scheme 1).…”