The method for the synthesis of ethyl 4-[3-(ethoxycarbonyl)-1-phenyl-1H-pyrazol-4-yl]-2-oxo/thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates was developed, and the bioactivity of the obtained compounds against infectious agents was predicted. Docking studies of the synthesised compounds were performed on pteridine reductase 1 (PTR1) of Leishmania, dihydrofolate reductase–thymidylate synthase of Trypanosoma cruzi, and human dihydrofolate reductase. The results demonstrated that the investigated compounds exhibit high affinity for these enzymes. Moderate selectivity relative to human DHFR was also observed. In addition, the predicted drug-likeness, ADME-Tox parameters, and toxicity profiles suggest the potential of the synthesised compounds for further pharmacological development.

The global rise of life-threatening diseases, particularly breast cancer, has emerged as a grave public health challenge. Recognizing the distinct structural demands of anti-breast cancer targets, we have synthesized Thiophene-DHPMs analogs by scaffold hopping approach to exhibit versatility having the ability to target proteins targets of cancer and their interactions contingent upon the various substitutions on them. We have harnessed MCRto synthesize novel Thiophene-DHPMs (4a-4d) derivatives introducing an efficient Biginelli protocol approach. All derivatives are characterized through techniques including FTIR and ¹H NMR and evaluated by in vitro SRB assay method on MCF-7 cell line, compared against positive control ADR. Molecular docking studies against kinesin spindle protein Eg5 (1Q0B) revealed superior binding interactions and docking scores (> 8 Kcal) compared to the prototype Eg5 inhibitor Monastrol. Compound 4a binds via Hydrogen bond interaction to target Eg5 with ALA-133, PRO-137, TYR-211 In vitro evaluation of results indicates that compound 4a found to be moderately active (GI₅₀ = -4.41) compared to positive control ADR (GI₅₀ = -7.76) against MCF-7 cells. Compound 4a demonstrates significant activity due to the presence of R=C2H5, X= S, and thiophene ring.

In the present work, synthesis of phthalimide and naphthalimide derived Biginelli compounds was performed. Allylation of phthalic & naphthalic anhydride, followed by ozonolysis resulted in the formation of N-phathalimido/naphpthalimido acetaldehyde (2 and 7). These aldehydes were subjected to Biginelli reaction using urea/thiourea and divergent β-keto esters in the presence of sulfated tin oxide (5 mol%) as catalyst in ethanol reflux to produce the corresponding dihydropyrimidinone compounds (5a-j and 8a-h). Additionally, both their antioxidant and anti-inflammatory functions were carried out. Compounds 5e, 5f, 5i, and 5j have shown potent to moderate potent activity for both antioxidant and anti-inflamamtory activities when compared to standard. Compounds 8c and 8g have shown potent antioxidant and anti-inflamamtory activities when compared to other compounds.