1,721,104 research outputs found
Design, Synthesis and Biological Screening of Novel 1,5-Diphenyl-3-(4-(trifluoromethyl)phenyl)-2-pyrazoline Derivatives
No full text1-Phenyl-5-substituted-3-(4-(trifluoromethyl)phenyl)-4,5-dihydro-1H-pyrazole derivatives were synthesized from chalcone derivatives. The structures of compounds were characterized by IR, H-1 NMR spectroscopic methods and elemental analysis. All compounds were evaluated for their in vitro antioxidant activity using DPPH and ABTS methods, anti-inflammatory activity using lipoxygenase inhibitory method and antidiabetic activity using the alpha-glucosidase inhibitory method. Especially, pyrazoline derivatives exhibited stronger anti-inflammatory activity than the reference drug indomethacin (IC50: 50.45 mu M) and their IC50 values were in the range of 0.68 and 4.45 mu M. In addition, the ADME properties of all chalcone and pyrazoline derivatives were calculated by Lipinski's and Veber's rules
A new approach in cancer treatment: poly (ADP-ribose) polymerase-1 inhibitors
No full textInternal and external factors can damage DNA, the genetic material. Numerous repair mechanisms, which can repair those damages, exist in the normal cell. One of those is called PARP-1 enzyme. PARP-1 transfers ADP-ribose subunits from nicotinamide adenine nucleotide to protein acceptor. Thus, single strand DNA breaks can be repaired. If PARP-1 inhibition occurs, single strand DNA breaks cannot be repaired and double strand DNA breaks can be formed. Eventually, cells undergo necrosis or apoptosis. The aim of cancer treatment is to inhibit the PARP-1 enzyme. For this purpose, many studies have been published over the last decade and currently PARP-1 enzyme inhibitors which are in the phase studies and which are waiting to be marketed are available. In this review, information are given for the mechanisms by which DNA damage is repaired, the protection mechanism of the genomic integrity of PARP enzyme family and chemical structure of PARP-1 inhibitors which are improved to use in cancer treatment
Design, synthesis and biological evaluation of some new 2-Pyrazoline derivatives as potential anticancer agents
No full textA new series of N-(4-(1-Phenyl-5-aryl-4,5-dihydro-1H-pyrazol-3-yl)phenyl)-4-substitutedbenzamide derivatives were designed and synthesized from new chalcone derivatives. All newly synthesized compounds were determined by using IR, H-1-NMR, C-13-NMR spectroscopic methods, elemental analysis and evaluated for their in vitro antiproliferative activities on HeLa, MCF-7, MKN-45 cancer cell lines and NIH-3T3 cell line using MTT assay. Expression of Bax and Bcl-2 proteins was detected by Western-blot analysis and caspase-3 enzyme activity was measured. Notably, compounds 1f and 2f showed a significant cytotoxic effect in all three cancer cells and did not display cytotoxicity on NIH-3T3 normal cells. (IC50 = 26.66 +/- 2.73 mu M on HeLa, IC50 = 9.41 +/- 2.19 mu M on MCF-7, IC50 = 5.17 +/- 3.54 mu M on MKN-45 for 1f. IC50 = 17.96 +/- 3.34 mu M on HeLa, IC50 = 0.69 +/- 0.13 mu M on MCF-7, IC50 = 0.88 +/- 0.16 mu M on MKN-45 for 2f.) Moreover, 1f and 2f upregulated protein expression level of Bax and downregulated protein expression level of Bcl-2 in cells. Similarly, caspase-3 activity was increased in cells via 1f and 2f. It can be concluded that 1f and 2f activated apoptosis by inducing mitochondrial apoptotic proteins in HeLa, MCF-7, MKN-45. This could be potentially new anti-cancer derivatives and used to contribute to new therapeutic development
Synthesis, biological evaluation and in silico studies of new pyrazoline derivatives bearing benzo[d]thiazol-2(3H)-one moiety as potential urease inhibitors
No full textSynthesis and anticancer activity of new carbohydrazide derivatives bearing furan moiety
No full textAntiproliferative activity of some tautomeric hydrazones derived from chalcones
No full textA new series of hydrazones synthesized from chalcones. Synthesized compounds have been characterized by IR, H-1-NMR and elemental analysis. Antiproliferative activity of compounds was investigated on Hela, A549, MCF7, HCC1937, MRC5 cells. All compounds exhibited cytotoxicity. Especially compounds 1b, 1c, 1f and 1i having 4-metylsulfonyl phenyl showed higher cytotoxicity against all of the cell lines compared to reference drug doxorubicin with low value of IC50=5,56-21,93 mu M. The most active compounds 1b, 1c, 1f and 1i were analyzed for their effect on autophagic processes. HCC1937 cells were treated with these compounds at IC50 concentration for 24 hours. An immunoblotting assay was performed to analysis autophagy markers and total polyubiquitinated protein levels. Compounds 1b, 1c, 1f and 1i significantly increased the conversion of LC3-I to LC3-II at IC50 concentration. None of the tested compounds changed the level of total polyubiquitinated proteins
Synthesis and biological evaluation of new pyrazolone Schiff bases as monoamine oxidase and cholinesterase inhibitors
No full textIn the current work, Schiff base derivatives of antipyrine were synthesized. The chemical characterization of the compounds was confirmed using IR, H-1 NMR, C-13 NMR and mass spectroscopies. The inhibitory potency of synthesized compounds was investigated towards acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and monoamine oxidases A and B (MAO-A and MAO-B) enzymes. Some of the compounds displayed significant inhibitory activity against AChE and MAO-B enzymes, respectively. According to AChE enzyme inhibition assay, compounds 3e and 3g were found as the most potent derivatives with IC50 values of 0.285 mu M and 0.057 mu M, respectively. Also, compounds 3a (IC50 = 0.114 mu M), 3h (IC50 = 0.049 mu M), and 3i (IC50 = 0.054 mu M) were the most active derivatives against MAO-B enzyme activity. So as to understand inhibition type, enzyme kinetics studies were carried out. Furthermore, molecular docking studies were performed to define and evaluate the interaction mechanism between compounds 3g and 3h and related enzymes. ADME (Absorption, Distribution, Metabolism, and Excretion) and BBB (Blood, Brain, Barier) permeability predictions were applied to estimate pharmacokinetic profiles of synthesized compounds
Design, synthesis, biological evaluation and molecular docking of novel molecules to PARP-1 enzyme
No full textPoly (ADP-ribose) polymerase (PARP) enzyme catalyzes the transfer of ADP-ribose into target proteins. Therefore, PARP is responsible for DNA repair, cell proliferation, and cell death. In this study, potential PARP enzyme inhibitors were designed and synthesized. The synthesized compounds were elucidated by Fourier-transform infrared spectroscopy, H-1 NMR, C-13 NMR, heteronuclear single-quantum correlation, and mass spectrometry, and their purity was checked via thin-layer chromatography, high-performance liquid chromatography, and elemental analysis. A total of 63 newly synthesized compounds were screened in terms of PARP inhibition by cellular PARylation assay in the HeLa cell line. It was found that 19 compounds significantly inhibited the H2O2-induced cellular PARylation. The chemosensitizer effect of these compounds in cancer cells treated with doxorubicin (doxo) was investigated. It was found that the combination of potent PARP inhibitors with doxo potentiated a cytotoxic effect, similar to that of olaparib. The results of the molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis revealed that compound 60 might be classified as a potential PARP inhibitor candidate. Taken together, all of the results suggested that carbohydrazide derivatives could be a promising lead for the treatment for cancer disorders
Design, Synthesis and Evaluation of the Biological Activities of Some New Carbohydrazide and Urea Derivatives
No full textObjectives: Urea and carbohydrazide derivatives are important compounds exhibiting cytotoxic activities. In this study, a series of new urea and carbohydrazide derivatives containing an pyridine ring were synthesized and evaluated for cytotoxic activity. Materials and Methods: The proposed structures of the synthesized compounds were confirmed using elemental analysis, IR, and H-1-NMR spectroscopic techniques. The cytotoxic potencies of synthesized compounds were determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) on BRCA mutant-carrying HCC1937 and Capan-1 cell lines, as well as on MCF7, HeLa, and MRC5 cells. Results: 3a, 3b, 3c and 3d showed cytotoxic activity against all cancer cell lines. Conclusion: Our data indicate that compounds 3a-d are more selective to cancer cells compared with nontumoral fibroblasts; however, these compounds are not more potent on HR defective cells with BRCA mutants
Novel 2,5-disubstituted-1,3,4-oxadiazole derivatives as MAO-B inhibitors: Synthesis, biological evaluation and molecular modeling studies
No full textThirty novel 2,5-disubstituted-1,3,4-oxadiazole derivatives bearing urea moiety were designed and synthesized. IR, 1H-NMR, 13C-NMR and mass spectroscopic methods and elemental analysis were used to confirm the structures of the compounds. Their monoamine oxidase inhibitory activity was determined against the MAO-A and MAO-B isoforms. None of the compounds showed the potent MAO-A inhibitory activity, while the MAO-B inhibition was significantly found in the range of 62 to 98%. Among them, the compounds H8, H9 and H12 bearing chloro substituent at the fourth position of phenylurea were found to show potent monoamine oxidase B inhibitory activity with IC50 values 0.039-0.066 mu M. To define and evaluate the interaction mechanism between compound H8 and monoamine oxidase B, molecular docking studies have been made
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