Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi

Abstract

In this study, we designed and synthesized a series of thiophen-2-iminothiazolidine derivatives from thiophen-2-thioureic with good anti-Trypanosoma cruzi activity. Several of the final compounds displayed remarkable trypanocidal activity. The ability of the new compounds to inhibit the activity of the enzyme cruzain, the major cysteine protease of T. cruzi, was also explored. The compounds 3b, 4b, 8b and 8c were the most active derivatives against amastigote form, with significant IC50 values between 9.7 and 6.03μM. The 8c derivative showed the highest potency against cruzain (IC50=2.4μM). Molecular docking study showed that this compound can interact with subsites S1 and S2 simultaneously, and the negative values for the theoretical energy binding (Eb=-7.39kcal·mol(-1)) indicates interaction (via dipole-dipole) between the hybridized sulfur sp(3) atom at the thiazolidine ring and Gly66. Finally, the results suggest that the thiophen-2-iminothiazolidines synthesized are important lead compounds for the continuing battle against Chagas disease.

Highly functionalized piperidines: Free radical scavenging, anticancer activity, DNA interaction and correlation with biological activity

“…Computational methodologies, such as molecular docking, have been employed to providing new scaffolds with high potency and good tolerance [23] . After molecular dynamic completion, the optimized ct-DNA structure with the lowest RMSD value was used in this study [24] .…”

Thiazolidinone-Related Heterocyclic Compounds as Potential Antitrypanosomal Agents

“…Different (thio)ureas/(thio)semicarbazides were reported as inhibitors of the trypanosome proliferation [110][111][112] and had shown high affinity to the antitrypanosomal targets: cruzain and rhodesain [109,113], cysteine proteases [114], etc. Different classes of "drug-like" molecules based on a thiazolidinone scaffold have been designed and synthesized in the process of search for antitrypanosomals [42,[115][116][117][118][119]. One of the most prominent directions is the conjugation of the thiazolidinone core with other different molecular fragments (mainly privileged substructures) [120,121] that proves the efficiency of a molecular hybridization approach and a hybrid pharmacophore approach for the design of new antitrypanosomals [122][123][124].…”

“…brucei allowed identifying a series of active compounds based on 2,4-diaminothiazoles, some of them possessing antitrypanosomal activity at the nanomolar range [140]. Combination of thiazolidine scaffold with a thiophene moiety yielded thiophen-2-iminothiazolidine hybrids that showed trypanocidal activity in vitro against T. cruzi (amastigote and trypomastigote forms) and cruzain inhibition activity [115].…”

Computer-Aided Design, Synthesis, and Antiviral Evaluation of Novel Acrylamides as Potential Inhibitors of E3-E2-E1 Glycoproteins Complex from Chikungunya Virus

“…Additionally, coupling constants (J) were determined in hertz (Hz). Moreover, signal multiplicities were attributed as singlet (s), broad singlet (br s), doublet (d), double-doublets (dd), triplet (t), triplet of doublets (td), quartet (q), and multiplet (m) [78,106]. Finally, all NMR spectra were treated and analyzed by using the academic licensed Bruker TopSpin ® software, version 4.0.7, 2019.…”