Synthesis, Biological Evaluation, Molecular Docking and DFT Study of Potent Antileishmanial Agents Based on the Thiazolo[3, 2‐a]pyrimidine Chemical Scaffold

Abstract

A series of 20 compounds having thiazolo[3, 2‐a]pyrimidine chemical scaffold were synthesized and evaluated for their antileishmanial activity against promastigotes of Leishmania donovani. Amongst all, two compounds showed promising antileishmanial activity in comparison to other compounds. Inhibitory concentration 50% (IC50) was calculated as 42.1 μM and 25.1 μM with selectivity index of 8.3 and 6.05, respectively against Miltefosine (reference drug) 37.78 μM with selectivity index of 2.05. To confirm the target of the these molecules, we modelled Leishmania donovani Ca2+ ion channel (LdCC) protein and performed the docking analysis of the best antileishmanial activity exhibiting inhibitors. The free energy of binding was observed as −10.2 and −9.6 kcal mol−1 in comparison to reference drug −6.2 kcal mol−1. It also makes several hydrogen bonds with our conserved residue Ser1655, Tyr1598 and Asn927. Furthermore, several hydrophobic contacts were also observed within the pocket. Finally, computational work employing density functional theory (DFT) was also carried out to investigate the electronic properties of the synthesized compounds. The in vitro and in silico activities conclusively revealed that our lead compounds may be used as a novel therapeutics against leishmaniasis.

Synthesis, spectroscopic characterization, density functional theory, molecular docking studies, antioxidant and antimicrobial potential of novel Schiff base macrocyclic complexes of bivalent manganese

“…The higher value of electronegativity for [Mn(N 8 MacL 3 )Cl 2 ] is responsible for its greater chemical reactivity. The complex [Mn(N 8 MacL 3 )Cl 2 ] is interacting more effectively in the biological environment, which is also shown by the significantly higher values of electronegativity 45 …”

“…more effectively in the biological environment, which is also shown by the significantly higher values of electronegativity. 45 The labeled structure of the macrocyclic complex [Mn (N 8 MacL 3 )Cl 2 ] is shown in Figure 9. The data of selected bond lengths and angles of macrocyclic ligands (N 8 MacL 1 -N 8 MacL 3 ) and their complexes [Mn(N 8 MacL 1 ) Cl 2 -Mn(N 8 MacL 3 )Cl 2 ] are listed in Tables 8 and 9.…”

A promising discovery of an anti-aging chemical conjugate derived from lipoic acid and sesamol established inDrosophila melanogaster

“…These values are too high, which indicates that the LSC has significant opportunity for increasing activity in the physiological system. 67 Further, the ESP surface mapping of the LSC facilitated the route for drug–protein interactions and drug–receptor interactions. In the LSC structure, the methylenedioxy bridge, carbonyl, and disulfide groups are active motifs for biological interactions.…”

Diversification Via Coupling Reactions and Biological Activities of Pyrimidine Derivatives

“…Among the investigated substances, two outperformed the others in the series regarding anti-leishmanial activity. [73] The researchers modeled the Leishmania donovani Ca 2 + ion channel (LDCC) protein, and a docking analysis was performed to confirm the target of these drugs. Our analysis set out to do just that to understand the binding interactions between the synthetic chemicals and the LDCC protein and shed light on the mechanism of action.…”