Identification, in-vitro anti-plasmodial assessment and docking studies of series of tetrahydrobenzothieno[2,3-d]pyrimidine-acetamide molecular hybrids as potential antimalarial agents

Biannual Account of Anti‐malarial Agents reported in 2021 and 2022: A Comprehensive Coverage

“…found the anti‐malarial activity of thieno[2,3‐ d ]pyrimidine‐acetamide against Pf W2 and Pf 3D7 strains (Figure 25). Compounds ( 103‐105 ) reported strong binding interactions with wild and mutant type Pf DHFR‐TS in docking analysis and in vitro study shown as the most potent anti‐malarial property with low toxicity and high selectivity [118] . Next, they also synthesized tetrahydrobenzo[4,5]thieno[2,3‐ d ]pyrimidines ( 106 ‐ 107 ) and reported anti‐plasmodial activity with IC 50 0.74–6.4 μM range against Pf W2 strain.…”

Is structural hybridization invoking new dimensions for antimalarial drug discovery research?

“…Dihydrofolate reductase (PfDHFR) inhibition makes pyrimidine, pyrimethamine, and cycloguanil antiplasmodial which can lead to the disturbance of DNA synthesis and the death of the rapidly proliferating cells. 44,45 The hybrids of pyrimidine with pyrazole, amodiaquine, etc. are available for treatment of malaria.…”

Reinvestigation of diphenylmethylpiperazine analogues of pyrazine as new class of Plasmodial cysteine protease inhibitors for the treatment of malaria

“…17 Le Manach, et al 18 identified a series of water-soluble 2-aminopyrazines as P. falciparum phosphatidylinositol 4-kinase (PfPI4K) inhibitors, with (4-(5amino-6-(4-(trifluoromethyl)phenyl)pyrazin-2-yl)phenyl) (piperazin-1-yl)methanone (C) as the most potent compound with an IC 50 value of 5.4 nM. Recently, Johnson, et al 19 designed a pyrazine-based series of new antimalarials and reported 3-(4-(difluoromethoxy)phenyl)-5-phenethoxy- [1,2,4] triazolo [4,3-a]pyrazine (D), as a potent molecule with IC 50 concentrations of 0.31 μM and 0.54 μM for Pf3D7 and PfDd2 strains, respectively.…”

“…A poor understanding of the biology of parasites, which can potentially lead to new drug targets, adds up to the existing challenges to control malaria. To counter drug resistance, several researchers are continuously striving to develop diverse classes of heterocyclic molecules, including quinolines, 1 thieno [2,3- d ]pyrimidine, 2 dipeptide-sulfonamides, 3 spirooxindoles, 4 pyrimidine, 5 and molecular hybrids. 6–8 The heterocyclic motif pyrazine exhibits diverse pharmacological properties and has been explored to develop antimycobacterial, antibacterial, antifungal, antidiabetic, diuretic, anticancer, antiviral, hypnotic, and analgesic agents.…”