Synthesis and antimalarial activity of N-benzylated (N-arylcarbamoyl)alkylphosphonic acid derivatives

Synthesis, Antimalarial Activity, and Docking Studies of Monocarbonyl Analogues of Curcumin

“…In silico exploration studies of the PfDXR active-site [20] revealed additional, adjacent binding pockets that could be explored. The presence of this additional binding pocket identified has prompted the de novo design of Nbenzylated phosphonate esters as potential antimalarials [21]. Figure 2.…”

Synthesis, Antiplasmodial and Antitrypanosomal Evaluation of a Series of Novel 2-Oxoquinoline-based Thiosemicarbazone Derivatives

“…The HeLa cells (Cellonex) were cultured using method described by Oderinlo et al and Adeyemi et al 30,31 Trypanosoma brucei brucei 427 trypomastigotes were cultured in Iscove's Modified Dulbecco's Medium (IMDM; Lonza) supplemented with 10 % fetal calf serum, HMI-9 supplement, 32 hypoxanthine and penicillin/streptomycin at 37°C in a 5 % CO 2 incubator. Serial dilutions of test compounds were incubated with the parasites in 96-well plates for 24 h and residual parasite viability in the wells determined by adding 20 µL of 0.54 mM resazurin in phosphate buffered saline (PBS) and incubating for an additional 24 h. Reduction of resazurin to resorufin by viable parasites was assessed by fluorescence readings (excitation 560 nm, emission 590 nm) in a Spectramax M3 plate reader.…”

“…IC 50 values were determined by plotting % viability vs. log[compound] and performing non-linear regression using GraphPad Prism (v. 5.02) software. 30,31…”

Synthesis and biological screening of diethyl [N-(thiazol-2-yl)carbamoyl]methylphosphonates

“…The enzyme,1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) regulates a non-mevalonate pathway in the biosynthesis of isoprenoid-derived compounds in Plasmodium falciparum (Pf), but is not found in humans 1,2 . This enzyme has been validated as a target for the development of antimalarial drugs capable of selectively inhibiting reduction of 1-deoxy-D-xylulose-5-phosphate 1 in resistant P. falciparum strains [3][4][5] . The naturally occurring antibiotic, fosmidomycin [3-(N-formyl-N-hydroxyamino)propylphosphonic acid 4,5 and its Nacetyl derivative, FR900098 2 6,7 , are known to inhibit PfDXR, and various analogues of these compounds have been prepared.…”

“…This enzyme has been validated as a target for the development of antimalarial drugs capable of selectively inhibiting reduction of 1-deoxy-D-xylulose-5-phosphate 1 in resistant P. falciparum strains [3][4][5] . The naturally occurring antibiotic, fosmidomycin [3-(N-formyl-N-hydroxyamino)propylphosphonic acid 4,5 and its Nacetyl derivative, FR900098 2 6,7 , are known to inhibit PfDXR, and various analogues of these compounds have been prepared. In our own group, research has focussed on the synthesis and antimalarial activity of phosphonated N-aryl-and N-heteroaryl-carboxamides, such as compound 3 8,9 and, more recently, phosphoramidate analogues 6 of fosmidomycin.…”