Hybrid PABA-glutamic acid conjugated 1,3,5-triazine derivatives: Design, synthesis, and antimalarial activity screening targeting Plasmodium falciparum dihydro folate reductase enzyme.

Despite the successful reduction in the malaria health burden in recent years, it continues to remain a significant global health problem mainly because of the emerging resistance to first-line treatments. Also because of the disruption in malaria prevention services during the COVID-19 pandemic, there was an increase in malaria cases in 2021 compared to 2020. Hence, the present study outlined the in silico study, synthesis, and antimalarial evaluation of 1,3,5-triazine hybrids conjugated with PABA-glutamic acid.

In silico screening, synthesis, and antimalarial evaluation of PABA substituted 1,3,5-triazine derivatives as Pf-DHFR inhibitors.

Objectives: Drug resistance in malaria parasites necessitates the development of new antimalarial drugs with unique mechanisms of action. In the present research work, the PABA conjugated 1,3,5-triazine derivatives were designed as an antimalarial agent.

Methods: In this present work, a library of two hundred-seven compounds was prepared in twelve different series such as [4A (1-23), 4B(1-22), 4C(1-21), 4D(1-20), 4E(1-19), 4F(1-18), 4G(1-17), 4H(1-16), 4I(1-15), 4J(1-13), 4K(1-12) and 4L(1-11) ] respectively using different primary and secondary aliphatic and aromatic amines.

Molecular docking and antimalarial evaluation of hybrid -aminobenzoic acid 1,3,5 triazine derivatives inhibition of -DHFR.

In this study, a structurally guided pharmacophore hybridization strategy is used to combine the two key structural scaffolds, -aminobenzoic acid (PABA), and 1,3,5 triazine in search of new series of antimalarial agents. A combinatorial library of 100 compounds was prepared in five different series as [ (-), (-), (-), (-) and (-)] using different primary and secondary amines, from where 10 compounds were finally screened out through molecular property filter analysis and molecular docking study as promising PABA substituted 1,3,5-triazine scaffold as an antimalarial agent. The docking results showed that compounds and exhibited good binding interaction with Phe58, IIe164, Ser111, Arg122, Asp54 (-424.

Molecular docking and antimalarial evaluation of novel -(4-aminobenzoyl)-l-glutamic acid conjugated 1,3,5-triazine derivatives as -DHFR inhibitors.

Unlabelled: Malaria has been a source of concern for humans for millennia; therefore in the present study we have utilized in-silico approach to generate diverse anti-malarial hit. Towards this, Molinspiration cheminformatics and Biovia Discovery Studio (DS) 2020 were used to conduct molecular modelling studies on 120 designed compounds. Furthermore, the TOPKAT module was used to evaluate the toxicity of the screened compounds.

Microwave synthesis and antimalarial screening of novel 4-amino benzoic acid (PABA)-substituted pyrimidine derivatives as dihydrofolate reductase inhibitors.

Unlabelled: Antimalarial drug resistance is a major threat due to the emerging resistance to all the available drugs in the market. In an approach to develop alternative drugs, a novel class of -DHFR inhibitors was developed using pyrimidine as the core nucleus and substituting the 4- and 6- positions with amines and 4-amino benzoic acid (PABA) to avoid the problem of drug resistance. The resultant compounds 3(a-j) after primary in silico screening and filtering were synthesized using microwave efficiently in high yield and reduced time period compared to conventional synthesis.