Microwave‐assisted synthesis of hybrid PABA‐1,3,5‐triazine derivatives as an antimalarial agent

Abstract

The present manuscript deals with the development of novel p-aminobenzoic acid (PABA) associated 1,3,5-triazine derivatives as antimalarial agents. The molecules were developed via microwave-assisted synthesis and structures of compounds were ascertained via numerous analytical and spectroscopic techniques. The synthesized compounds were also subjected to ADMET analysis. In a docking analysis, the title compounds showed high and diverse binding affinities towards wild (−162.45 to −369.38 kcal/mol) and quadruple mutant (−165.36 to −209.47 kcal/mol) Pf-DHFR-TS via interacting with Phe58, Arg59, Ser111, Ile112, Phe116. The in vitro antimalarial activity suggested that compounds 4e, 4b, and 4h showed IC 50 ranging from 4.18 to 8.66 μg/ml against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum. Moreover, compounds 4g, 4b, 4e, and 4c showed IC 50 ranging from 8.12 to 12.09 μg/ml against chloroquine-resistant (Dd2) strain. In conclusion, our study demonstrated the development of hybrid PABA substituted 1,3,5-triazines as a novel class of Pf-DHFR inhibitor for antimalarial drug discovery.

CuO nanoparticles for green synthesis of significant anti-Helicobacter pylori compounds with in silico studies

“…As a result, it is possible to conclude that the XRD reveals a single phase monoclinic structure of CuO-NPs. The end result was comparable to statistics reported elsewhere 22 .…”

“…A wide variety of computational biology programs are available through MOLIN-SPIRATION that help with the manipulation and processing of molecules. These tools include SMILES and Sdfile conversion, molecule normalization, tautomer generation, molecule fragmentation, calculation of various molecular properties required for QSAR, molecular modeling and drug design, high-quality molecule depiction, and molecular database instruments assisting substructure and likeness searches 22,33 .…”

Design and development of novel N‐(4‐aminobenzoyl)‐l‐glutamic acid conjugated 1,3,5‐triazine derivatives as Pf‐DHFR inhibitor: An in‐silico and in‐vitro study

“…The chloroquine‐sensitive (3D7) and resistant (Dd2) strain of P. falciparum were routinely maintained in continuous culture following Trager and Jensen method [ 25 ] medium, RPMI (Roswell Park Memorial Institute)‐1640 supplemented with 25 mmol 4‐(2‐hydroxyethyl)‐1‐piperazine‐ethane sulfonic acid (HEPES), 2% D(+)‐glucose, 0.23% sodium bicarbonate and 10% heat‐inactivated human serum or 0.5% Albumax II, lipid‐rich bovine serum albumin with 0.01% hypoxanthine. The asynchronous parasites of P. falciparum were synchronized after 5% d ‐sorbitol treatment to obtain only the ring stage parasitized cells.…”

“…The chloroquine-sensitive (3D7) and resistant (Dd2) strain of P. falciparum were routinely maintained in continuous culture following Trager and Jensen method [25]…”

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

“…Hence based on the structural features of WR99210 and folic acid, PABA‐glutamic acid conjugated 1,3,5‐triazine hybrid molecule was designed as new analogues of folic acid to check their efficacy against resistant Pf strains (Yuthavong et al, 2012). Since 1,3,5‐triazine nucleus is present in many antifolates and has been matured into an indispensable heterocyclic scaffold with a broad spectrum of biological profile, including antibacterial and antimicrobial (Al‐Zaydi et al, 2017; Xia et al, 2023; Younis et al, 2022), anticancer (Guo & Diao, 2020; Junaid et al, 2020), antioxidant (Havránková et al, 2020), anti‐parkinsonism (Masih et al, 2020, 2021), antidiabetic (Wang et al, 2019), and antimalarial (Bhat et al, 2015; Gravestock et al, 2011; Kashyap et al, 2021; Klenke et al, 2003) properties. In this study, a compound library was designed and screened through in silico screening and molecular docking for synthesis.…”