Exploring the antioxidant, antimicrobial, cytotoxic and biothermodynamic properties of novel morpholine derivative bioactive Mn(ii), Co(ii) and Ni(ii) complexes - combined experimental and theoretical measurements towards DNA/BSA/SARS-CoV-2 3CLPro.

A novel class of bioactive complexes (1-3) [MII(L)2(bpy)], where, L = 2-(4-morpholinobenzylideneamino)phenol, bpy = 2,2'-bipyridine, MII = Mn (1), Co (2) or Ni (3), were assigned to octahedral geometry based on analytical and spectral measurements. Gel electrophoresis showed that complex (2) demonstrated significant DNA cleavage activity compared to the other complexes under the action of oxidation agent (H2O2). The DNA binding constant properties measured by various techniques were in the following sequence: (2) > (3) > (1) > (HL), which suggests that the complexes might intercalate DNA, a possibility that is also supported by their biothermodynamic characteristics. The binding constant results for BSA from electronic absorption and fluorometric titrations demonstrate that complex (2) exhibits the highest binding effectiveness among them all, which means that all the compounds could interact with BSA through a static approach, additionally supported by FRET measurements. DFT and docking calculations were employed to realize the electronic structure, reactivity, and interaction capability of all substances with DNA, BSA, and the SARS-CoV-2 main protease. These binding energies fell within the ranges -7.7 to -8.5, -8.2 to -10.1 and -6.7 to -9.3 kcal mol-1, respectively. The higher reactivity of the complexes than the ligand is supported by FMO theory. The in vitro antibacterial, cytotoxicity, and radical scavenging characteristics revealed that complexes (2-3) have better biological efficacy than the others. The cytotoxicity and binding properties also show good correlation with the partition coefficient (log P), which is encouraging because all of the experimental findings are closely correlated with the theoretical measurements.

SARS-CoV-2 Mpro binding profile and drug-likeness of two novel thiazole derivatives: structural elucidation, DFT studies, ADME-T and molecular docking simulations.

Two novel thiazole derivatives, ethyl 5-((4-fluorophenyl)carbamoyl)-thiazole-4-carboxylate (2b) and ethyl 5-(p-tolylcarbamoyl)thiazole-4-carboxylate (6b) have been synthesized, and their crystal structures determined by X-ray diffraction. To rationalize their structure, reactivity and druggability, we have performed a series of separate, but complementary studies. Hirshfeld surface and 2D-fingerprint plots were first scrutinized to qualitatively unveil all the intermolecular interactions that ensure their crystal packing. Moreover, topological electron density parameters established from the quantum theory of atoms-in-molecules (QTAIM) and Reduced Density Gradient (RDG) were later relied on to characterize the chemical bonding of these species, in terms of the nature and magnitude of noncovalent interactions developed within their monomeric and dimeric forms. In both structures, C-H…O hydrogen bonds are found to be stronger than other noncovalent interactions. Furthermore, H…H bonding contacts and non-conventional C-H…O hydrogen bonds both exhibit a closed shell nature, and play in crucial role in the stability of the novel thiazoles. The isosurfaces in the intermolecular region furnished by NCI molecular diagram signifies the existence of weak noncovalent interactions. Finally, the potential inhibitory activity of the titled compounds and their drug-likeness are demonstrated by molecular docking and ADME-T calculations respectively. Both compounds adhere to the Lipinski's rule of five and present encouraging pharmacokinetic properties and safety profiles.Communicated by Ramaswamy H. Sarma.