Design, synthesis and molecular docking studies of some morpholine linked thiazolidinone hybrid molecules

Abstract

A novel series of morpoline linked thiazolidione hybrid molecules targeting bacterial enoyl acyl carrier protein (Enoyl-ACP) reductase were designed and synthesized through a three step reaction protocol, which involves simple reaction setup and moderate reaction conditions. The synthesized molecules were characterized with FT-IR, 1 H NMR, 13 C NMR and HRMS techniques. In vitro susceptibility tests against some Gram positive (Staphylococcus aureus and Bacillus subtilis) and Gram negative bacteria (Escherichia coli and Pseudomonas aeruginosa) gave highly promising results. Most of the molecules were found to be active against the tested bacterial strains. The most potent molecule (S2B7) gave MIC value of 2.0 µg/mL against Escherichia coli that was better than the reference drug streptomycin. Structure activity relationship showed nitro and chloro groups are crucial for bioactivity if present at meta position of arylidene ring in designed molecules. Molecular docking simulations against multiple targets showed that the designed molecules have strong binding affinity towards Enoyl-ACP reductase. Binding affinity of -8.6 kcal/mol was predicted for S2B7. Van der Waals forces, hydrogen bonding and hydrophobic interactions were predicted as the main forces of interaction.

Rationale design and synthesis of some novel imidazole linked thiazolidinone hybrid molecules as DNA minor groove binders

“…However, in spite of their huge pharmacophoric potential, there have been very few attempts to design hybrid molecules containing both imidazole and thiazolidinone moieties [7,[15][16]. Keeping this in view and continuing our effort of building novel biologically active molecules [17,18], here we report some novel imidazole linked thiazolidinone hybrid molecules with the hypothesis that the resulting molecules would bear broad spectrum antibiotic applicability.…”

“…FT-IR (KBr, ν, cm -1 ): 3390, 3273 (NH, thiourea), 3063 (CHAr). 1 H NMR (500 MHz, DMSO-d6, δ, ppm): 9.50 (s, 1H, 11 NH), 7.79 (s, 1H, 9 NH), 7.62 (s, 1H, 1 CH), 7.40 (dd, 2H, 13,17 CH, J = 7.44, 1.04 Hz), 7.30 (td, 2H, 14,16 CH, J = 8.28, 7.44), 7.14 (d, 1H, 4 CH, J = 7.54 Hz), 7.09 (td, 1H, 15 CH, J = 7.36,7.32 Hz), 6.89 (d, 1H, 3 CH, J = 7.36 Hz), 4.01 (t, 2H, 6 CH2, J = 6.96,7.0 Hz), 3.49 (t, 2H, J = 4.96, 6.0 Hz, 8 CH2), 2.02 (m, 2H, 7 CH2). 13…”

Recyclization of morpholinochromonylidene–thiazolidinone using nucleophiles: facile synthesis, cytotoxic evaluation, apoptosis, cell cycle and molecular docking studies of a novel series of azole, azine, azepine and pyran derivatives

“…Hence, research for the invention of novel agents for treating cancer is of prime importance. 2 Combination of morpholine and thiazolidinone rings in one molecular structure has been proved for its potency as antimicrobial, [3][4][5][6] anticancer, 6 antioxidant, 7 antihistaminic and anticholinergic agents 8 as well as a neuroprotective agent against cerebral ischemia reperfusion. 9 On the other hand, chromone compounds have long gained interest as highly reactive molecules that can be used as precursors in the synthesis of a wide variety of heterocycles.…”