Dataset Information

Molecular Docking Analysis of Pyrimethamine Derivatives with Plasmodium falciparum Dihydrofolate Reductase.

ABSTRACT: DHFR from Pf is a known target for malaria. There is a continued effort for the design and development of the potent inhibitor for PfDHFR in the control of malaria. Therefore it is of interest to screen PfDHFR with the derivatives of Pyrimethamine. The results show that the compound CID 10476801 has lowest docked energy (-11.48 kcal/mol) with protein likely to be a drug candidate, probably inhibiting PfDHFR structure. Residues of PfDHFR protein involved in the formation of hydrogen bonds with compound CID 10476801 are confirmed to be ASP54. The findings provide new insights into development of potent chemotherapeutic drug for combating malaria.

SUBMITTER: Singh IV

PROVIDER: S-EPMC6077817 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Molecular Docking Analysis of Pyrimethamine Derivatives with Plasmodium falciparum Dihydrofolate Reductase.

Singh Indra Vikram IV Mishra Sanjay S

Bioinformation 20180531 5

DHFR from Pf is a known target for malaria. There is a continued effort for the design and development of the potent inhibitor for PfDHFR in the control of malaria. Therefore it is of interest to screen PfDHFR with the derivatives of Pyrimethamine. The results show that the compound CID 10476801 has lowest docked energy (-11.48 kcal/mol) with protein likely to be a drug candidate, probably inhibiting PfDHFR structure. Residues of PfDHFR protein involved in the formation of hydrogen bonds with co ...[more]

PMID: 30108420

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Project description:Malaria caused by Plasmodium falciparum infects roughly 30,000 individuals in Haiti each year. Haiti has used chloroquine (CQ) as a first-line treatment for malaria for many years and as a result there are concerns that malaria parasites may develop resistance to CQ over time. Therefore it is important to prepare for alternative malaria treatment options should CQ resistance develop. In many other malaria-endemic regions, antifolates, particularly pyrimethamine (PYR) and sulphadoxine (SDX) treatment combination (SP), have been used as an alternative when CQ resistance has developed. This study evaluated mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes that confer PYR and SDX resistance, respectively, in P. falciparum to provide baseline data in Haiti. This study is the first comprehensive study to examine PYR and SDX resistance genotypes in P. falciparum in Haiti.DNA was extracted from dried blood spots and genotyped for PYR and SDX resistance mutations in P. falciparum using PCR and DNA sequencing methods. Sixty-one samples were genotyped for PYR resistance in codons 51, 59, 108 and 164 of the dhfr gene and 58 samples were genotyped for SDX resistance codons 436, 437, 540 of the dhps gene in P. falciparum.Thirty-three percent (20/61) of the samples carried a mutation at codon 108 (S108N) of the dhfr gene. No mutations in dhfr at codons 51, 59, 164 were observed in any of the samples. In addition, no mutations were observed in dhps at the three codons (436, 437, 540) examined. No significant difference was observed between samples collected in urban vs rural sites (Welch's T-test p-value = 0.53 and permutations p-value = 0.59).This study has shown the presence of the S108N mutation in P. falciparum that confers low-level PYR resistance in Haiti. However, the absence of SDX resistance mutations suggests that SP resistance may not be present in Haiti. These results have important implications for ongoing discussions on alternative malaria treatment options in Haiti.

Dataset Information

Molecular Docking Analysis of Pyrimethamine Derivatives with Plasmodium falciparum Dihydrofolate Reductase.

Publications

Molecular Docking Analysis of Pyrimethamine Derivatives with Plasmodium falciparum Dihydrofolate Reductase.

Similar Datasets

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