New pyrimidine-N-ß-D-glucosides: synthesis, biological evaluation, and molecular docking investigations.

In this study, syntheses of new pyrimidine-coupled N-ß-glucosides and tetra-O-acetyl derivatives were carried out. All glycoconjugates were investigated in comparison with known chemotherapeutic agents in terms of their antimicrobial and anticancer functions and DNA/protein binding affinities. Spectral data showed that all glycoside derivatives were obtained by diastereoselectivity as ß-anomers. Both tested groups exhibited strong antiproliferative activity (2.29-66.84 µg/mL), but some of them had sufficiently ideal % cytotoxicity values (10.01%-16.78%). And also all synthetic compounds exhibited remarkable antibacterial activity against human pathogenic bacteria. Binding of these compounds to CT-DNA resulted in significant changes in spectral properties, consistent with groove binding. Molecular docking studies of some compounds revealed that the docking score, complex energy, and MM-GBSA ΔGBind energy values were consistent with the experimental results, which showed that the new compounds were potent chemotherapeutic agents. Overall bioactivity results suggest that these compounds may be candidates as new chemotherapeutic agents and deserve further pharmacological evaluation.

New chalcone derivative, ethyl 2-(4-(3-(benzo[b]thiophen-2-yl)acryloyl)phenoxy)acetate: synthesis, characterization, DFT study, enzyme inhibition activities and docking study.

Chalcone derivative, ethyl 2-(4-(3-(benzo[b]thiophen-2yl)acryloyl)phenoxy)acetate (I), was synthesized. Compound I was characterized by proton and carbon-13 nuclear magnetic resonance (1H- and 13C- NMR), fourier transform infrared (FTIR) and mass (LC-ESI-MS/MS) spectroscopic methods. Density Functional Theory (DFT) calculations for compound I were performed at B3LYP/6-311++G(d,p) level. Optimized geometry, frontier molecular orbitals (HOMO; highest occupied molecular orbital; LUMO: lowest unoccupied molecular orbital), IR and NMR parameters of compound I were obtained. The evaluations reveal that the calculation results support the experimental results. The inhibition effects of compound I on cholinesterases and GST enzyme were investigated. Ki and inhibition concentration (IC50) values were calculated separately. Ki values of compound I were found for GST 14.19 ± 2.15, for AChE 11.13 ± 1.22 and for BChE 8.74 ± 0.76 recpectively. The docking analysis of compound I supported the enzym inhibition activity exhibiting high inhibition constant and binding energy for three receptors. Compound I is strongly bound to AChE, huBChE and Glutathione S-transferase with binding energies -11.24, -8.56 and -10.39 kcal/mol, respectively.Communicated by Ramaswamy H. Sarma.

Synthesis, biological evaluation (antioxidant, antimicrobial, enzyme inhibition, and cytotoxic) and molecular docking study of hydroxy methoxy benzoin/benzil analogous.

In this work, due to the biological activity evaluation, a series of hydroxy methoxy benzoins (1-8), benzils (10-16) and methoxy benzoin/benzil-O-ß-d-glucosides (17-28) were synthesized. Antioxidant (FRAP, CUPRAC, DPPH), antimicrobial (16 microorganisms, and two yeast), enzyme inhibition (α-amylase, α-glucosidase, AChE, BChE, and tyrosinase) of all synthesized benzoin/benzil analogs were investigated. Benzoins (1-8) showed the most effective antioxidant properties compared to all three methods. Compound 28 against α-amylase, compound 9 against α-glucosidase, compound 11 against AChE, compound 2 against BChE, and compound 13 against tyrosinase showed the best activities with the better or similar IC50 values as used standards. Hydroxy methoxy benzoin compounds (1-8) among all four groups were seen as the most effective against the tested microorganism. Molecular docking analysis showed that all tested compounds 1-28 (0.01-2.22 µM) had the best binding affinity against AChE enzyme. Cytotoxic effects of the many of compounds (1-16, 21, and 24) also investigated and it was found that they caused different effects in different cells. The LDH tests of compounds 1a + b, 4, 7, 8, 9, 11, 12, 21, and 24, seemed to be effective compared to the positive control cisplatin. The cytotoxicity of compounds 6 (9.24%) for MCF7 cancer cells, 8 (5.16%) and 4 (8.26%) for HT29 cancer cells, 24 (9.84%) for Hep3B cells and 8 (8.52%), 7 (5.70%), 4 (6.94) and 9 (7.22%) for C6 cells were at normal values. And also cytotoxic activity of four compounds (5, 9, 21, and 24) among the all synthetic groups, were evaluated to the HeLa and RPE. Compound 5 showed anticancer activity on HeLa and RPE cancer cells as much as or better than cisplatin which was used as standard.

Synthesis of novel 1,2,3 triazole derivatives and assessment of their potential cholinesterases, glutathione S-transferase enzymes inhibitory properties: An in vitro and in silico study.

In this study, new 1,2,3-triazole derivatives containing chalcone core (1-7) were synthesized. Obtained compounds were characterized by IR, 1H NMR, 13C NMR, and mass studies. Characterized compounds (1-7) inhibitory effects were tested against the glutathione S-transferase (GST), acetylcholinesterase (AChE), and Butyrylcholinesterase (BChE). Their Ki values were in the range of 5.88-11.13 µM on AChE, 5.08-15.12 µM on BChE, and 9.82-13.22 µM on GST. Remarkable inhibitory effects were obtained against three tested metabolic enzymes. Also, binding scores of the best-inhibitors against AChE, BChE, and GST enzymes were detected as -9.969 kcal/mol, -10.672 kcal/mol, and -8.832 kcal/mol, respectively. Isoindoline-1,3-dione and benzothiophene moieties played a critical role in the inhibition of AChE and BChE enzymes, respectively. Phenylene and triazole moieties had the most important interactions for inhibition of the GST enzyme. Therefore, in vivo and in silico results indicated that these compounds can be considered in drug design processes for the treatment of some diseases including Alzheimer's disease (AD), leukemia, and some type of cancer.

Synthesis of peripheral and non-peripheral substituted metallophthalocyanines containing (E)-3-(5-bromo-2-hydroxphenyl)-1-o-tolyprop-2-en-1-one: Investigation of the photophysical and photochemical properties.

In this study, the novel peripherally (5-7) and non-peripherally (9-11) metallo (zinc, magnesium and lead) phthalocyanine derivatives were synthesized from their (E)-4-(4-bromo-2-(3-oxo-3-o-tolyprop-1-enyl)phenoxy) substituted phthalonitrile precursors (4 and 8). These novel phthalocyanine derivatives including chalcone groups were characterized by spectroscopic techniques such as FT-IR, UV-vis, 1H NMR, 13C NMR and MALDI-TOF mass spectra. In the next stage, the photophysical and photochemical properties of synthesized compounds were searched in DMSO which is not cause toxic effects at a certain concentration in biological applications. As a result of investigations, it was determined that phthalocyanine complexes did not demonstrate aggregation in DMSO solutions.

Synthesis of hydroxy benzoin/benzil analogs and investigation of their antioxidant, antimicrobial, enzyme inhibition, and cytotoxic activities.

In this study, hydroxy benzoin ( 1-7 ), benzil ( 8-14 ), and benzoin/benzil-O-ß-D-glucosides ( 15-25 ) were synthesized to investigate their biological activities. An efficient method for synthesizing hydroxy benzoin compounds ( 1 - 7 ) was prepared from four different benzaldehydes using an ultrasonic bath. Then, antioxidant (FRAP, CUPRAC, and DPPH), antimicrobial (3 Gram (-), 4/6 Gram (+), one tuberculosis and one fungus), and enzyme inhibition (acetylcholinesterase, butyrylcholine esterase, tyrosinase, α-amylase, and α- glucosidase) for the all synthesized compounds ( 1-25 ) were evaluated. And also, four most active compounds ( 4 , 12 , 18a+b , and 25 ) from each group were evaluated to the human cervical cancer cell line (HeLa) and anticancer screening tests against the human retinal normal cell line (RPE). Compound 4 showed HeLa and RPE cancer cell activities as much as cisplatin. The synthesized compounds were characterized by spectroscopic methods (NMR, FT-IR, UV, LC-QTOF-MS) and the ACD NMR program's help.

Novel 2-amino-4-aryl-6-pyridopyrimidines and N-alkyl derivatives: Synthesis, characterization and investigation of anticancer, antibacterial activities and DNA/BSA binding affinities.

A series of new 2-amino-4-aryl-6-pyridopyrimidines, and their N-alkyl bromide derivatives were designed and synthesized by employing methyl substituted azachalcones. These novel compounds were evaluated and compared to the well-known chemotherapeutics in terms of their anti-cancer and anti-microbial functions, and their DNA/protein binding affinities. In order for the cell proliferation, cytotoxicity and microdilution features to be observed, various cancer cell lines (Hep3B, A549, HeLa, C6, HT29, MCF7) were treated with 2-amino-4-aryl-6-pyridopyrimidines (1-9) and their N-alkyl bromide derivatives (2a-c, 3a-c,5a-c,6a-c, 8a-c, 9a-c). Studies on the cells revealed that both pyrimidines and their alkyl derivatives (i) have a high anti-proliferative and anti-microbial activities, (ii) cause cell rounding, cytoplasmic blebs, and anomalous globular structure, and (iii) strongly bound to DNA/BSA macromolecules. Especially the length of the alkyl chain of the N-alkyl bromides has an increasing effect on the antiproliferative, antibacterial and cytotoxic functions, also DNA/protein binding affinity. Those results indicate the novel compounds to be promising antiproliferative agents, and their anti-cancer potential makes them candidates to be used for cancer therapy.

Synthesis and electrochemical properties of copper(II), manganese(III) phthalocyanines bearing chalcone groups at peripheral or nonperipheral positions.

In this study, new chalcone compound 1 , new phthalonitrile derivatives 2 and 3, new copper(II), manganese(III) phthalocyanines bearing chalcone groups at peripheral or nonperipheral positions were synthesized. Electrochemistry of tetra-(4-{(2 E )-3-[2-fluoro-4-(trifluoromethyl)phenyl]prop-2-enoyl}phenoxy) substituted Co(II)Pc and Mn(III)Pcs were studied with cyclic voltammetry (CV) to determine the redox properties of the phthalocyanines. According to the results, while the CuPcs 2a and 3a showed two Pc based reduction reactions and one Pc based oxidation reaction, MnPcs 2b and 3b gave two metal-based reduction reactions. All the redox processes are shifted toward positive potentials as a result of the increased electron-withdrawing ability of the trifluoromethyl substituents.

Synthesis and biological evaluation of new 2,4,6-trisubstituted pyrimidines and their N-alkyl derivatives.

A series of new 2,4,6-trisubstituted pyrimidines and their N-alkyl bromide derivatives were prepared based upon methoxy substituted azachalcones as the starting materials. All newly synthesized compounds were screened for their anti-proliferative, cytotoxic, antibacterial activities and DNA/protein binding affinity. In vitro cell proliferation inhibitory and cell cytotoxic effects of 2,4,6-trisubstituted pyrimidines (1-9) and their N-alkyl bromide derivatives (2a-c, 3a-c,5a-c,6a-c, 8a-c, 9a-c) were obtained with the help of the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) cell proliferation, LDH cytotoxicity detection, and microdilution assays. The antimicrobial activity for these compounds was also evaluated following the European Pharmacopoeia 8.0 protocol. The interactions of these compounds with DNA or bovine serum albumin were investigated by the spectrophotometric titration method. When the cytotoxic analysis and anticancer properties of the compounds were examined, most of the compounds significantly exhibited an anti-proliferative potency on cancer cells (IC50 ∼ 2-10 µg/mL) and caused a cytotoxic effect as low as control drugs, 5-fluorouracil, and cisplatin (∼7-15%). Because the compound-DNA adducts are hyperchromic or hypochromic, they caused variations in their spectra. This situation shows they can be linked to DNA by the groove binding mode at a binding constant range of 2.0 × 104 and 2.4 × 105 M-1. The antimicrobial screening results revealed that our new compounds for some human Gram(+) and Gram(-) pathogen bacteria showed remarkable activity with MIC values between <7.81 and 125 µg/mL. Overall, incorporation of alkyl chain to pyrimidines in the generation of N-alkyl bromides has resulted in showing differences in DNA/protein binding affinity, along with anti-proliferative and cytotoxic activity in favor of new compounds.

Synthesis of Novel Pyrazolines, Their Boron-Fluorine Complexes, and Investigation of Antibacterial, Antioxidant, and Enzyme Inhibition Activities.

New 3,5-disubstituted-2-pyrazoline derivatives (4-6), their boron-fluorine complexes (boron (3-(2'-aminophenyl),5-(2'-/3'-/4'-pyridyl)pyrazoline, BOAPPY) (7-9) and boron 1,2'-diazaflavone complex (BODAF) (11) were synthesized starting from azachalcones (1-3) to diazaflavone (10), respectively. Biological evaluation of compounds 4-9 and 11 showed remarkable antioxidant, antibacterial, and acetylcholinesterase and tyrosinase enzyme inhibition activities. All newly synthesized compounds 4-9 and 11 showed respectable antibacterial effect with minimum inhibitory concentrations in the range of 4.7-150 µg/mL.

Synthesis, antibacterial and antioxidant activities of new 1-alkyl-4-(1-alkyl-4-oxo-1,4-dihydroquinolin-2-yl)pyridinium bromides.

New 1-alkyl-4-(1-alkyl-4-oxo-1,4-dihydroquinolin-2-yl)pyridinium bromides (3a-k) were synthesized from 1,4'-diazaflavone [2-pyridin-4-ylquinolin-4(1H)-one] and evaluated for antibacterial and antioxidant activities. A rapid one-pot preparation of 1,4'-diazaflavone (2) was done from 2'-amino substituted chalcone (1) by intramolecular Michael addition using solvent-free microwave heating. New N,N'-dialkyl substituted (C5-C15) 1,4'-diazaflavonium bromides were synthesized from compound 2 with corresponding alkyl halides. Compounds 3a-k were active against six bacteria (MIC: 7.8-500.0 µg/mL). They also showed good antioxidant activities in DPPH scavenging (SC50: 45-133 µg/mL) and ferric reducing/antioxidant power (14-141 µM TEAC) tests. The biological activities decreased as alkyl chain length increased. The reason behind the obvious negative effect of alkyl chain elongation is unclear and requires investigations about the intermolecular interactions of these pyridinium salts with bioassay components.

Composition and antimicrobial activity of the essential oils from flowers of Senecio othonnae, s. racemosus, and s. nemorensis.

The chemical composition of the essential oils of Senecio othonnae, S. racemosus, and S. nemorensis obtained by hydrodistillation of fresh flowers were analysed by GC-FID and GC-MS. A total of seventy-six compounds were identified, constituting over 83.1%, 97.7% and 86.8% of the total oil composition of the flowers of S. othonnae, S. racemosus, and S. nemorensis. The main components of the oils were caryophyllene oxide (18.6%), (E)-beta-farnesene (21.6%), and gamma-curcumene (42.8%), respectively. Sesquiterpene hydrocarbons were the main group of constituents of all three species, forming 34.6%, 73.2%, and 81.8% of the oils, respectively. The oils of S. othonnae, and S. nemorensis showed antimicrobial activity against Bacillus cereus, Staphylococcus aureus, Enterococcus faecalis, and Candida tropicalis, but that of S. racemosus was only active against Candida tropicalis.