Synthesis of Novel Hydrazide-Hydrazone Compounds and In Vitro and In Silico Investigation of Their Biological Activities against AChE, BChE, and hCA I and II.

The abnormal levels of the human carbonic anhydrase isoenzymes I and II (hCA I and II) and cholinesterase enzymes, namely, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), are linked with various disorders including Alzheimer's disease. In this study, six new nicotinic hydrazide derivatives (7-12) were designed and synthesized for the first time, and their inhibitory profiles against hCA I, hCA II, AChE, and BChE were investigated by in vitro assays and in silico studies. The structures of novel molecules were elucidated by using spectroscopic techniques and elemental analysis. These molecules showed inhibitory activities against hCA I and II with IC50 values ranging from 7.12 to 45.12 nM. Compared to reference drug acetazolamide (AZA), compound 8 was the most active inhibitor against hCA I and II. On the other hand, it was determined that IC50 values of the tested molecules ranged between 21.45 and 61.37 nM for AChE and between 18.42 and 54.74 nM for BChE. Among them, compound 12 was the most potent inhibitor of AChE and BChE, with IC50 values of 21.45 and 18.42 nM, respectively. In order to better understand the mode of action of these new compounds, state-of-the-art molecular modeling techniques were also conducted.

Design, spectroscopic characterization, in silico and in vitro cytotoxic activity assessment of newly synthesized thymol Schiff base derivatives.

Cancer is a global public health problem affecting millions of people every year. New anticancer drug candidates are needed to overcome the resistance to drugs used in the treatment of various types of cancer. In this study, two new series of benzenesulfonate-based thymol derivatives (14-19 and 20-25) were synthesized for the first time as promising chemotherapeutic agents and characterized using FT-IR, 1D NMR (1H- and 13C-NMR, APT, DEPT 135), 2D NMR (HETCOR and HMBC), and elemental analysis (CHNS). Antiproliferative activity of the molecules was determined against cancer cell lines, namely, the human lung adenocarcinoma cell line (A549) and the colorectal adenocarcinoma cell line (DLD-1), using MTT method for both 48 and 72 h. Compounds (14-25) showed cytotoxic activities against A549 with IC50 values ranging from 9.98 to 81.83 µM, respectively, compared to cisplatin (6.65 µM). These compounds exhibited antiproliferative activities against DLD-1 cancer cells at concentrations ranging from 4.29 to 53.62 µM, respectively, compared to cisplatin (9.91 µM). Especially, compound 16 displayed significant cytotoxicity on A549 and DLD-1 cancer cells with IC50 values of 9.98 and 10.75 µM, respectively. Finally, molecular docking studies were performed with Bcl-2, VEGFR-2, EGFR, and HER2 targets using the Schrödinger 2021-2 Maestro Glide program. The binding energy values and binding interactions of compounds 16 and 22 were determined to be the result of their interactions with these targets. Schrödinger 2021-2 Qikprop wizard drug similarity ratios and ADME prediction of all compounds 14-25 were also calculated.Communicated by Ramaswamy H. Sarma.

Novel chiral Schiff base Palladium(II), Nickel(II), Copper(II) and Iron(II) complexes: Synthesis, characterization, anticancer activity and molecular docking studies.

In this study, two chiral Schiff base ligands (L1 and L2) were synthesized from the condensation reaction of (S)-2-amino-3-phenyl-1-propanol with 2-hydroxybenzaldehyde and 2-hydroxy-1-naphthaldehyde as metal precursors for the preparation of transition metal complexes with Pd(II), Fe(II), Ni(II) and Cu(II). The compounds were characterized by using X-ray (for L1-Pd(II)), NMR, FT-IR, UV-Vis, magnetic susceptibility, molar conductivity, and elemental analysis. The in vitro cytotoxic effects of ligands (L1 and L2) and their metal complexes on colon cancer cells (DLD-1), breast cancer cells (MDA-MB-231) and healthy lung human cell lines were investigated by using the 3-(4,5-dimethylthiazol-2-yl)-2,5­diphenyl tetrazolium bromide (MTT) assay. Among the synthesized compounds, L1-Pd(II) was particularly found to be the most potent anticancer drug candidate in this series with IC50 values of 4.07, and 9.97 µM in DLD-1 and MDA-MB-231 cell lines, respectively. In addition, molecular docking results indicate that Glu122, Asn103, Ala104, Lys126, Phe114, Leu123, and Lys126 amino acids are the binding site of the colon cancer antigen protein, in which the most active complex, L1-Pd(II) can inhibit the current target.

Biological activity and molecular docking studies of some N-phenylsulfonamides against cholinesterases and carbonic anhydrase isoenzymes.

In this research, a series of N-phenylsulfonamide derivatives (1-12) were designed, synthesized, and investigated for their inhibitory potencies against carbonic anhydrase isoenzymes I, II, and IX (hCA I, hCA II, and hCA IX) and cholinesterases (ChE), namely, acetylcholinesterase and butyrylcholinesterase. These compounds, whose inhibition potentials were evaluated for the first time, were characterized by spectroscopic techniques (1 H- and 13 C-NMR and FT-IR). CA isoenzyme inhibitors are significant therapeutic targets, especially owing to their preventive/activation potential in the therapy processes of some diseases such as cancer, osteoporosis, and glaucoma. On the other hand, Cholinesterase inhibitors are valuable molecules with biological importance that can be employed in the therapy process of Alzheimer's patients. The results showed that the tested molecules had enzyme inhibition activities ranging from 9.7 to 93.7 nM against these five metabolic enzymes. Among the tested molecules, the methoxy and the hydroxyl group-containing compounds 10, 11, and 12 exhibited more enzyme inhibition activities when compared to standard compounds acetazolamide, sulfapyridine, and sulfadiazine for CA isoenzymes and neostigmine for ChE, respectively. Of these three molecules, compound 12, which had a hydroxyl group in the para position in the aromatic ring, was determined to be the most active molecule against all enzymes. In silico work, molecular docking has also shown similar results and is consistent with the experimental data in the study. As a result, we can say that some of the tested molecules might be used as promising inhibitor candidates for further studies on this topic.

Synthesis, characterization, and biological evaluation of some novel Schiff bases as potential metabolic enzyme inhibitors.

In this study, a series of novel Schiff base derivatives containing a pyrazolone ring (2a-e) were designed, successfully synthesized for the first time, and characterized by elemental analysis and some spectroscopic methods. These compounds were tested for their inhibitory activities on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and the human carbonic anhydrase isoenzymes I and II (hCA I and II). All synthesized molecules indicated significant inhibition effects with IC50 values ranging from 14.15 to 107.62 nM against these enzymes. Compound 2d showed the most potent inhibitory activity among the tested molecules toward AChE and BChE (IC50 = 15.07 and 14.15 nM) compared to the standard drug neostigmine. We determined that the IC50 values of the tested molecules ranged between 16.86 and 57.96 nM for hCA I and 15.24-46.21 nM for hCA II. As a consequence, we may say that some of the Schiff base derivatives may be used as potential drug candidates in later studies.

Magnetite nanoparticles grafted with murexide-terminated polyamidoamine dendrimers for removal of lead (II) from aqueous solution: synthesis, characterization, adsorption and antimicrobial activity studies.

In this study, new, efficient, eco-friendly and magnetically separable nanoadsorbents, MNPs-G1-Mu and MNPs-G2-Mu, were successfully prepared by covalently grafting murexide-terminated polyamidoamine dendrimers on 3-aminopropyl functionalized silica-coated magnetite nanoparticles, and used for rapid removal of lead (II) from aqueous medium. After each adsorption process, the supernatant was successfully acquired from reaction mixture by the magnetic separation, and then analyzed by employing ICP-OES. Chemical and physical characterizations of new nanomaterials were confirmed by XRD, FT-IR, SEM, TEM, and VSM. Maximum adsorption capacities (qm) of both prepared new nanostructured adsorbents were compared with each other and also with some other adsorbents. The kinetic data were appraised by using pseudo-first-order and pseudo-second-order kinetic models. Adsorption isotherms were found to be suitable with both Langmuir and Freundlich isotherm linear equations. The maximum adsorption capacities for MNPs-G1-Mu and MNPs-G2-Mu were calculated as 208.33 mg g-1 and 232.56 mg g-1, respectively. Antimicrobial activities of nanoparticles were also examined against various microorganisms by using microdilution method. It was determined that MNPs-G1-Mu, MNPs-G2-Mu and lead (II) adsorbed MNPs-G2-Mu showed good antimicrobial activity against S. aureus ATTC 29213 and C. Parapsilosis ATTC 22019. MNPs-G1-Mu also showed antimicrobial activity against C. albicans ATTC 10231.

Covalent Immobilization of Candida rugosa Lipase on Epichlorohydrin-Coated Magnetite Nanoparticles: Enantioselective Hydrolysis Studies of Some Racemic Esters and HPLC Analysis.

In this study, a new biocatalyst was prepared by immobilizing Candida rugosa lipase epichlorohydrin-functionalized onto the surface of the nanoparticles. Magnetite nanoparticles were obtained by chemical co-precipitation method of Fe2+ and Fe3+, and then the prepared uncoated and coated nanoparticles were characterized by XRD, FT-IR and TGA. Lipase was covalently attached to activated nanoparticles. The catalytic properties of free and immobilized lipases were determined. It was found that the optimum temperature for free and immobilized lipases was 30 °C and 35 °C, respectively. The optimum pH values were found to be 7.0 and 8 for free and immobilized lipases, respectively. Immobilized lipase was found to retain significant activity even after the seventh use. In the final section of the study, optically pure compounds were obtained by carrying out the enantioselective hydrolysis studies of racemic esters by using immobilized lipase. Enantiomeric excesses of the products in the enantioselective hydrolysis of racemic ibuprofen and naproxen methyl ester and racemic butyl mandelate were determined to be 94.93, 77.30 and 68.15, respectively.

Design, synthesis and biological evaluation of novel nitroaromatic compounds as potent glutathione reductase inhibitors.

Discovery of GR inhibitors has become very popular recently due to antimalarial and anticancer activities. In this study, the synthesis and GR inhibitory capacities of novel nitroaromatic compounds (NCs) (1-3) were reported. Some commercially available molecules were also tested for comparison reasons. The novel NCs were obtained in high yields using simple chemical procedures and exhibited much potent inhibitory activities against GR at low micromolar concentrations with K(i) values ranging from 0.211 to 4.57 µM as compared with well-known agents. Inhibition mechanism was assessed as being due to occlusion of the active site entrance by means of the NCs. Molecular docking results have shown that docking poses of ligands are able to construct binding interactions with the essential amino acids.

Resolution of (+/-)-beta-methylphenylethylamine by a novel chiral stationary phase for Pirkle-type column chromatography.

In this study, a new Pirkle-type chiral column stationary phase for resolution of beta-methylphenylethyl amine was described by using activated Sepharose 4B as a matrix, L-tyrosine as a spacer arm, and an aromatic amine derivative of L-glutamic acid as a ligand. The binding capacities of the stationary phase were determined at different pH values (pH = 6, 7, and 8) using buffer solutions as mobile phase, and enantiomeric excess (ee) was determined by HPLC equipped with chiral column. The ee was found to be 47%.