Investigation of Newly Synthesized Fluorinated Isatin-Hydrazones by In Vitro Antiproliferative Activity, Molecular Docking, ADME Analysis, and e-Pharmacophore Modeling.

In this study, we investigated the in vitro antiproliferative activities and performed computational studies of newly synthesized fluorinated isatin-hydrazones. The chemical structures of the synthesized compounds were confirmed by FT-IR, 1D NMR (1H- and 13C NMR and APT), 2D NMR (HETCOR and HMBC), and elemental analysis. All compounds (1-15) were tested in human lung (A549) and liver (HepG2) cancer cell lines for 72 h. The compounds were screened against a healthy embryonic kidney cell line (HEK-293T) under the same conditions to determine their toxic effects. According to the results obtained, one of the compounds, in particular, compound 8 was effective at inhibiting the growth of cancerous cells, and its effects on both cancer cell lines were similar to IC50 values of 42.43 and 48.43 µM for A549 and HepG2, respectively. Compound 8, which was determined to be the best anticancer agent in vitro, was chosen to interact with the target via molecular docking. This selected ligand (compound 8) interacted with the targets 4HJO, 4ASD, 3POZ, and 7TZ7, and docked into the active sites. The docking score, Glide energy, and Glide emodel values were calculated and determined to be lower than those of the reference compound cisplatin. The pharmacokinetic properties, stability, and drug-likeness parameters of all designed compounds were estimated using SwissADME. Finally, the binding affinities of compound 8 for all four targets were calculated using the MM-GBSA method.

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, Synthesis, and In Silico and In Vitro Cytotoxic Activities of Novel Isoniazid-Hydrazone Analogues Linked to Fluorinated Sulfonate Esters.

Cancer is a life-threatening disease, and significant efforts are still being made to treat it. In this study, we synthesized and characterized novel hybrid molecules (10-18) containing hydrazone and sulfonate moieties and tested their cell growth inhibitory effect on human colon cancer cells (DLD-1), human prostate cancer cells (PC3), and human embryonic kidney cells (HEK-293T) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method for 72 h. In cell culture studies, all tested hybrid molecules except for 12 and 13 showed significant cytotoxic activities at a micromolar level with IC50 values in the range of 10.28-214.0 µM for the PC3 cell line and 13.49-144.30 µM for the DLD-1 cell line. Compounds 4 (10.28 µM) and 5 (11.22 µM) demonstrated the highest cytotoxicity against the PC3 cell line. Against the DLD-1 cell line, compounds 1 (22.53 µM), 4 (13.49 µM), 5 (19.33 µM), 6 (17.82 µM), 8 (24.71 µM), 9 (17.56 µM), and 10 (17.90 µM) in the series showed anticancer activity at lower micromolar levels compared to cisplatin (26.70 µM). Moreover, the study was handled computationally, and molecular docking studies were performed for compounds 1, 4, and 5 for PC3-FAK and PC3-Scr and compounds 4, 6, and 9 for the DLD-1-TNKS target. In this study, compound 4 was found to be the most effective and promising molecule for both targets.

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.

Intercalation of pyrazolone-based oxalamide metal complexes into Na-montmorillonite for catalytic liquid-phase oxidation of phenol using H2O2.

The intercalation of pyrazolone-based oxalamide metal complexes into Na-montmorillonite (Na-MMT) for catalytic liquid-phase oxidation of phenol using H2O2 was undertaken by a flexible ligand method using metal ions including Mn(II), Zn(II), and Sn(II). First, the metal ions were exchanged with the sodium ions of Na-MMT, and then these metal ions were complexed with a new pyrazolone-based oxalamide ligand. The intercalated metal complexes were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy, elemental analysis, and thermogravimetric analysis. Phenol was successfully oxidized by heterogeneous catalysts based on Mn(II), Zn(II), and Sn(II) pyrazolone-based oxalamide complexes intercalated into Na-MMT. These heterogeneous catalysts catalyze the liquid-phase oxidation of phenol using H2O2 to catechol as the major product and hydroquinone and benzoquinone as the minor products. The Mn(II) and Zn(II) complexes intercalated into Na-MMT showed better activity than the Sn(II) complex intercalated into Na-MMT and the reaction without the catalyst. It has been shown that some metal ion complexes intercalated into Na-MMT are active catalysts for liquid-phase oxidation of phenol with hydrogen peroxide.

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.

Synthesis of novel chiral metal complexes derived from chiral thiosemicarbazide ligands as potential antioxidant agents.

Two new chiral thiosemicarbazide ligands and their Cu (II), Ni (II), Pd (II), and Zn (II) complexes were synthesized and characterized by nuclear magnetic resonance (NMR) (only for ligand), Fourier transform infrared (FT-IR), ultraviolet visible (UV-Vis), mass, and elemental analysis. The antioxidant activity of ligands and their metal complexes was examined. It was found that the antioxidant activity of metal complexes was better than their ligands. In addition, the antioxidant activity, as reflected by free radical scavenging, was evaluated. Besides, Pd (II) complexes exhibited better antioxidant activity than Ni (II), Cu (II), and Zn (II) complexes. Therefore, complexes (3a-Pd and 3b-Pd) can be used as an antioxidant agent or antioxidant test standard.

Synthesis of Novel Chiral Sulfonamide-Bearing 1,2,4-Triazole-3-thione Analogs Derived from D- and L-Phenylalanine Esters as Potential Anti-Influenza Agents.

Novel enantiopure 1,2,4-trizole-3-thiones containing a benzensulfonamide moiety were synthesized via multistep reaction sequence starting with D-phenylalanine methyl ester and L-phenylalanine ethyl ester as a source of chirality. The chemical structures of all compounds were characterized by elemental analysis, UV, IR, (1) H NMR, (13) C NMR, 2D NMR (HETCOR), and mass spectral data. All compounds were tested in vitro antiviral activity against a broad variety of DNA and RNA viruses and in vitro cytostatic activity against murine leukemia (L1210), human T-lymphocyte (CEM) and human cervix carcinoma (HeLa) cell lines. Although enantiopure 1,2,4-triazole-3-thione analogs in (R) configuration emerged as promising anti-influenza A H1N1 subtype in Madin Darby canine kidney cell cultures (MDCK), their enantiomers exhibited no activity. Especially compounds , , , , and (EC50 : 6.5, 6.1, 2.4, 1.6, 1.7 µM, respectively) had excellent activity against influenza A H1N1 subtype compared to the reference drug ribavirin (EC50 : 8.0 µM). Several compounds have been found to inhibit proliferation of L1210, CEM and HeLa cell cultures with IC50 in the 12-53 µM range. Compound and in (R) configuration were the most active compounds (IC50 : 12-22 µM for and IC50 : 19-23 µM for ). Chirality 28:495-513, 2016. © 2016 Wiley Periodicals, Inc.