Search

Some metabolic enzyme inhibitors can be used as Multi-target-Directed-Ligands (MTDL) in Medicinal chemistry therefore, synthesis and determination of alternative inhibitors are essential. In this study, novel bisnapthoquinone derivatives (5a-o) were synthesized through a multi-component cascade reaction of two molecules of 2-hydroxy-1,4-naphthoquinone with an aromatic aldehyde in basic media using triethylamine as a catalyst. This novel heterocyclic derivatives (5a-o) are applied to inhibit the carbonic anhydrase (hCA I and hCA II) isoform in low levels of nano molecules with Ki values exist between 4.62 ± 1.01 to 70.45 ± 9.03 nM for hCA I and for hCA II which is physiologically dominant Kis values are in the range of 5.61 ± 1.04 to 73.26 ± 10.25 nM. Further these novel derivatives (5a-o) efficiently inhibit AChE with Ki values in the range of 0.13 ± 0.02 to 3.16 ± 0.56 nM. The compounds are also applied for BChE with Ki values varying between 0.50 ± 0.10 to 9.23 ± 1.15 nM. For α-glycosidase, the most efficient Ki values of 5e and 5f are 76.14 ± 9.60 and 95.27 ± 12.55 nM respectively. Finally, molecular docking calculations against enzymes (acetylcholinesterase, butyrylcholinesterase, and the human carbonic anhydrase I and II) are compared using biological activities of heterocyclic derivatives. After these calculations,an ADME/T analysis is performed to study the future medicinal use of heterocyclic derivatives from lawsone.

Bicyclic structures were synthesized by LACASA-DA cycloaddition reaction using (S)-BINOL as a chiral inductor. The N-2 pyridazine position was protected; the hydroxyl group was carbonylated to form the new bicyclic structure. The protective group was removed, the double bond dehydroxylated leading to the target compound. Removing of the protective group was performed using newly found ecofriendly catalyst for N-Boc deprotection. The obtained features from the model against AChE enzyme suggest that a lower the size of the ring, number of –NH-NH- groups, number of secondary aromatic amines, number of aromatic ketone groups may contribute to the inhibitory activity. The features obtained from the model against BChE enzyme suggest that the sum of topological distances between two nitrogen atoms, number of secondary aromatic amides, may be more favorable for inhibition. The features obtained from selectivity-based model suggest that the number of aromatic ethers, unsaturation content related to their molecular size and molecular shape may be more specific for the inhibition of the AChE enzyme in comparison to the BChE enzyme. Similarly, these aromatic structures inhibited the α-glucosidase enzyme at the micromolar level due to its structural feature. Inhibition values were found to be statistically significant, especially for cholinesterase enzymes. Molecular docking method was used to compare the biological activities of molecules against enzymes. The enzymes used in this study are α-glycosidase, butyrylcholinesterase, acetylcholinesterase, respectively. ADME/T analysis was performed to use some bicyclic molecules as drugs in the future.

This study shows the synthesis and characterization of 4,5-bis(4-propionylphenoxy)phthalonitrile (2) and its octa-substituted phthalocyanine derivatives [ZnPc(3), CuPc(4), and CoPc(5)]. A combination of standard spectroscopic techniques has characterized the newly synthesized phthalonitrile derivative and phthalocyanines. The aggregation behaviors of new octa-substituted phthalocyanines have been evaluated by ultraviolet-visible (UV-vis) spectroscopy. The metal ion-sensitive behaviors of new octa-substituted phthalocyanines in the presence of soft metal ions have been performed by UV-vis and fluorescence spectrophotometer. The quenching efficiency (K-sv) of Ag+ ions against ZnPc(3) was found using the Stern-Volmer equation. The binding constant (K-a) and binding stoichiometry (n) of ZnPc(3) with Ag+ ions were calculated using the modified Benesi-Hildebrand equation. Sensitive protonation behaviors of octa-substituted phthalocyanines have been investigated by titration experiments as well as computational calculations. The ZnPc(3) and CuPc(4) were exhibited H-type aggregation behaviors toward Ag+ ions. However, the protonation of octa-substituted zinc and copper phthalocyanine during the titration with HCl caused J-type self-aggregation properties. In vitro antioxidant properties of the new compounds were investigated by the radical scavenging ability of 1,1-diphenyl-2-picrylhydrazyl (DPPH), chelating ability to ferrous ions, and reducing power methods. Additionally, in vitro antibacterial activities of the octa-substituted phthalocyanines were determined. Finally, optimized structures of novel compounds [(2), ZnPc(3), CuPc(4), and CoPc(5)] were obtained on the HF (Hartree-Fock), B3LYP (Becke, 3-parameter, Lee-Yang-Parr), M06-2X methods with 3-21 g, 6-31 g and SDD basis set. Then, biological activities of novel phthalonitrile and its phthalocyanine derivatives toward breast, liver, and lung cancer proteins were compared with molecular docking studies.

The anti-corrosion potency of three synthesized 8-hydroxyquinoline derivatives, namely 5-(azidomethyl)-7-(morpholinomethyl)quinolin-8-ol (HM1), 2-(8-hydroxy-7-(morpholinomethyl)quinolin-5-yl)acetonitrile (HM2), 5-(azidomethyl)-7-(piperidin-1-ylmethyl)quinolin-8-ol (HM3) in hydrochloric acid for mild steel was investigated using weight loss and electrochemical techniques. Potentiodynamic polarization (PDP) data reveal that all three compounds were cathodic inhibitors, with HM3 presentation significant mixed-type effect at high inhibitor concentrations (10(-3) M). Electrochemical impedance spectroscopy (EIS) data reveal better adsorption of compounds species on MS surface at increased inhibitor concentrations with HM1, HM2 and HM3 reaching a maximum efficiency of 90, 89 and 88%. The three compounds HM1, HM2 and HM3 were inclined towards the Langmuir adsorption-isotherm by spontaneous chemical-physical adsorptions of inhibitors on the mild steel surface. The correlation between the electronic properties and inhibition efficacies of the tilted inhibitors was determined by using simple linear regression technique. Electronic properties were calculated for neutral and protonated forms in a polarizable continuum model using the DFT method at the B3LYP/6-311 + G (d, p) level of theory. The active adsorbed sites of HM1-HM3 on the metal surface were determined by analyzing their corresponding electrostatic surface potentials (ESP). Furthermore, molecular dynamics simulations have been performed to illustrate the most conceivable adsorption configuration between the inhibitors and metal surface. (C) 2020 Published by Elsevier B.V.