فهرست مطالب ali almasirad

In this work, a novel series of mefenamic acid analogs were developed and synthesized with the goal of developing a lead chemical that has anti-inflammatory efficacy and avoids the adverse effects of NSAIDs. Molecular docking analysis was performed by recruiting the ligands, COX-1 and COX-2 to identify the best-fitted molecule using AutoDock software. Afterwards, the compounds were synthesized and analyzed. To assess the drug's efficacy, the compounds were subjected to in vivo analgesic and anti-inflammatory experiments. Most of synthesized ligands have greater binding free energy than mefenamic acid on COX-1. When compared to the positive control, the compounds 2-(2,3-dimethylphenylamino)-N-(2-(3,5-di-tert-butyl-4-hydroxyphenyl)-4-oxothiazolidin-3-yl) benzamide, 2-(2,3-dimethylphenylamino)-N-(2-(4-fluorophenyl)-4-oxothiazolidin-3-yl)benzamide, 2-(2, 3-dimethylphenylamino)-N-(4-oxo-2-p-tolylthiazolidin-3-yl) benzamide and 2-(2,3-dimethylphenylamino)-N-(2-(4-chlorophenyl)-4-oxothiazolidin-3-yl) benzamide, 2-(2,3-dimethylphenylamino)-N-(2-(4-nitrophenyl)-4-oxothiazolidin-3-yl)benzamide demonstrated a larger or comparable proportion of analgesic and anti-inflammatory action respectively. Furthermore, the selected compounds “2-(2,3-dimethylphenylamino)-N-(2-(3,5-di-tert-butyl-4-hydroxyphenyl)-4-oxothiazolidin-3-yl) benzamide”, and “2-(2,3-dimethylphenylamino)-N-(4-oxo-2-p-tolylthiazolidin-3-yl) benzamide” seemed to have the least ulcerogenic activity. These findings show that some of the newly created mefenamic acid analogs may be selected as lead compounds due to their significant biological properties without ulcerogenic activity.

Hydrazones are an important class of bioactive drugs that have attracted much attention .One of the domains in this category of compounds is the synthesis of new hydrazone derivatives from NSAIDs, which are supposed to be more effective than the previous synthesized derivatives in terms of effect strength and severity of the complications. Many compounds of different chemical derivatives are designed and synthesized to treat various diseases, among which hydrazones are included, and their anti-cancer effects have been reported so far .The aim of this study was to investigate the hepatotoxicity profile of 4-chlorobenzolidin-hydrazine-naproxen derivatives and compare it with the main drug, naproxen. 120 fish specimens of Trichogaster trichopterus with average weight of 2.4±1 gr in 8 treatments were divided into control groups, control1 (intact), control2 (DMSO) and treatment groups receiving 10, 20, 30 mg/kg of naproxen and 10, 20, 30 mg/kg of hydrazine naproxen derivatives. These concentrations were selected according to previous works and related articles. After anesthetizing the fishes, liver tissue and liver enzymes were studied in treatment groups and the groups receiving the drug compared with control groups. The statistical results of the level of liver enzymes between control groups and treatments showed a significant difference (P<0/05). Histopathological examination of the liver tissue of the treatments indicated that the liver tissue had undergone a major change in the high doses of both drugs. The results showed that naproxen and hydrazine naproxen derivatives affect liver tissue and liver enzymes by increasing doses and increased sinusoidal spacing, and adipose vacuoles in liver.

The effect of liver ultrastructure and changes of liver enzymes with hydrazone derivative 2-phenylthiobenzoic acid as a new anti-inflammatory and its comparison with mefenamic acid was investigated in three spotted gourami fish.

120 pieces of Trichogaster trichopterus female fish with an average weight of 1.93 ± 0.43 g were purchased from from ornamental fish farm and divided into eight groups of 15 including the intact control group, DMSO solvent control, six treatment groups receiving mefenamic acid and hydrazone derivative with a dose of 10, 20 and 30 mg/kg. Data analysis was done using SPSS26 software with one-way analysis of variance (ANOVA) and Tukey's test at P≥0.05.

The results showed that in the highest dose of mefenamic acid and hydrazone derivative, the hepatosomatic index decreased significantly compared to the control treatments (P<0.05). ALP and ALT increased significantly in all mefenamic acid and hydrazone derivative treatments compared to control treatments (P<0.05). The highest ALT was measured in medium dose of mefenamic acid and hydrazone derivative and the highest AST was measured in low dose of mefenamic acid and hydrazone derivative (P<0.05). Liver histology with optical microscope showed that in the control treatments, liver sinusoids had a normal shape and a normal trend, while in the treatments of mefenamic acid and hydrazone derivative, expansion and disorder of the sinusoids occurred. In the examination of the electron microscope, dissociation was observed in the cell membrane and cytoplasm in the treatments of mefenamic acid and hydrazone derivative.

both Mefenamic acid and hydrazone derivative cause liver damage. In all three doses, mefenamic acid has more tissue and cell damage than the hydrazone derivative, and the hydrazone derivative is more favorable in terms of toxic profile.

Considering various studies implying anticancer activity of the hydrazone and oxamide derivatives through different mechanisms such as kinases and calpain inhibition, herein, we report the synthesis, characterization, and evaluation of the antiproliferative effect of a series of hydrazones bearing oxamide moiety compounds (7a-7n) against a panel of cancer cell lines to explore a novel and promising anticancer agent (7k).

Experimental approach:

 Chemical structures of the synthesized compounds were confirmed by FTIR, 1HNMR, 13C-NMR, and mass spectra. The antiproliferative activity and cell cycle progression of the target compound were investigated using the MTT assay and flow cytometry.

Compound 7k with 2-hydroxybenzylidene structure was found to have a significant in vitro anti-proliferative influence on MDA-MB-231 (human adenocarcinoma breast cancer) and 4T1 (mouse mammary tumor) cells as the model of triple-negative breast cancer, with the IC50-72 h values of 7.73 ± 1.05 and 1.82 ± 1.14 µM, respectively. Following 72-h incubation with compound 7k, it caused MDA-MB-231 cell death through G1/S cell cycle arrest at high concentrations (12 and 16 µM).

Conclusion and implications:

 Conclusively, this study for the first time reports the anti-proliferative efficacy of compound 7k possessing 2-hydroxyphenyl moiety, which may serve as a potent candidate in triple-negative breast cancer treatment.

Effective anticonvulsant drugs each selectively suppress the abnormal activity of neurons to some degree. However, their mechanism of action and efficacy differ in different types of epilepsy disorders.

Investigation of histological effects of 4chloro-N (2-(4-methoxyphenil)-4-oxotiazolidin-3-yl)-2-phenoxybenzamid compared to Diazepam as a reference drug on Trichogaster trichopterus ‘s liver which has done at the fish lab of Islamic Azad University.

In this study, 150 fish specimens with an average weight of 2 ± 0.5 gr were bought from Khan-mahi fish farm. This study was performed on 4 treatment groups (1, 3, 5, 7 mg/kg b.w.) and three controls including, control 1 (intact), control 2 (solvent tween 80), reference control (Diazepam 3 mg/kg.b.w). Before dropping fishes into the aquariums, dechlorination of water was performed in 24 hours, and physicochemical factors were measured. Injections were performed every other day for 20 days and all the treatments were anatomized and their livers put into the fixative to check by optical and electron microscope later.

The results showed that the ALT, AST and ALP were changed in controls to treatments. These results showed a significant difference between the control and the treatment groups (P≤0.05) Microscopic images also showed membrane changes, rupture, gaps between sinusoids, and necrosis at a dose of 5 mg /kg body weight and was in a dose-dependent.

Melphalan is a chemotherapy agent and used for treating of metastatic melanoma and breast cancer. However, the side effect of this compound have been limited its clinical care. Parthenolide, a sesquiterpene lactone is a bioactive compound from Tanacetum parthenium medicinal plant and have anti-leukemia properties. Despite the many advantages of sesquiterpene terpene lactones, these compounds have two obvious drawbacks: non-specificity for cancer cells and low solubility in water. Therefore, the aim of this study is to synthesis of melphalan and parthenolide hybride using conjugation method to enhance the higher potency to anticancer drug. Meanwhile, the cytotoxicity activity of this compound has been tested against breast cancer cell line (MDA-MB-231). Subjects and

In order to synthesis of mentioned compound, the melphalan as an anticancer drug have been conjugated to parthenolide sesquiterpene lactone by aza-Michael reaction. Then, the cytotoxicity activity of this compounds have been tested by alamar blue assay.

The parthalan product synthesis of melphalan anticancer drug and parthenolide sesquiterpene have been analysed and identified by LC-MS. The cytotoxicity activity results indicated that cell viability of cancer cell (MDA-MB-231) have been decreased in dose dependent manner and the IC50 of parthalan, parthenolide and synthesized hybrid were reported with respective values of 13/5, 24 and 23 μg/ml.

The overall results of this research demonstrated that parthenolide-melphalan hybrid induce significantly enhanced the higher potency of parthenolide.

Despite the advances made in research on cancer, there is still no effective way to treat this condition. A number of compounds including hydrazone derivatives have been increasingly investigated as anticancer agents. So, in this study a series of novel hydrazone derivatives were designed and synthesized as potential anticancer compounds and their cytotoxic effects were further evaluated.

The designed hydrazone compounds (1-9) were synthesized in three steps and their structures were characterized by different instrumental analysis methods. The cytotoxic activity was measured using MTT assay at 48 and 72 h on human breast, colon and liver cancer cell lines.

The obtained percentage of cytotoxicity indicated that some compounds were potent against cancer cell lines and the most effective incubation time was after 72 h of treeatment. Among the synthesized compounds, compounds 3 and 6 revealed the considerable cytotoxic activity on breast, liver and colon cells after 72 h of treatment ranging from 60 to 80%.

The results obtained in this section can be used as the starting point for the development of new cancer chemotherapy agents

Metal nanoparticles (NPs) offer a wide variety of potential applications in pharmaceutical sciences due to the unique advances in nanotechnology research. In this work, bimetal Ag-Au alloy NPs were prepared and their combinations with other antibiotics were tested against Staphylococcus aureus. Firstly, Ag-Au alloy NPs with Au/Ag molar ratio of 1:1 was fabricated and was purified by agarose gel electrophoresis system. The morphology and size of the purified NPs were confirmed by transmission electron microscopy. Chemical composition and surface chemistry of these NPs were studied with atomic absorption spectophotometry and Fourier transforms infrared spectroscopy, respectively. The size of purified Ag-Au alloy NPs was less than 200 nm. Also the presence of organic compounds with a hydroxyl residue was detected on the surface of these purified NPs. In next step the effect of purified Ag-Au alloy NPs on the antibacterial activity of different antibiotics was evaluated at sub-inhibitory content (5 μg/disk) using disk diffusion method against S. aureus. Ag NPs and Au NPs were also tested at same content (5 μg) using mentioned method. The most enhancing effect of Ag-Au alloy NPs was observed for penicillin G and piperacillin. No enhancing effects on the antibacterial activity of different antibiotics were observed at 5 μg/disk for the mono-metal nanoparticles (Ag NPs and Au NPs) against S. aureus. These results signify that the Ag-Au alloy NPs potentiates the antimicrobial action of certain antibiotics suggesting a possible utilization of this nano material in combination therapy against resistant S. aureus.

The uses of non-steroidal anti-inflammatory drugs (NSAIDs) are limited by a variety of side effects. So research on preparing new analgesic agents is important. According to some reports about the analgesic activity of hydrazide and hydrazine derivatives a new series of these compounds were synthesized in order to obtain new analgesic compounds. The final compounds 10a-10e and 15a-15d were prepared by condensation of corresponding hydrazides 7 and 8with different aldehydes 9a-9e. The structures of all synthesized compounds were confirmed by means of FT-IR, 1H-NMR and Mass spectra. All compounds were evaluated for their analgesic activities by abdominal constriction test (writhing test). Most of the synthesized compounds induced significant reduction in the writhing response when compared to control and compound 15was more potent than mefenamic acid in the writhing test.

A series of phenoxybenzylidene aroylhydrazine derivatives were synthesized and their structures were confirmed using FT-IR and 1H-NMR spectroscopy. Analgesic profiles of all compounds were examined using abdominal constriction test (writhing test). Most of synthesized compounds induced significant reduction in the writhing response as compared with controls. The most active compounds exhibited an analgesic activity comparable with that of mefenamic acid.

A series of new 2-(phenylthio) benzoylaryl hydrazones were synthesized by acid-catalyzed condensation of hydrazide 3 with corresponding aldehydes. The chemical structures of the compounds were elucidated by FT-IR, 1H-NMR and Mass spectra. All newly synthesized compounds were evaluated for their antimycobacterial activities against Mycobacterium tuberculosis H37Rv using the microplate alamar blue assay (MABA). Compounds 4f (5-Nitro-2-furyl analogue) and 4g (5-Nitro-2-thienyl analogue) showed antimycobacterial activity with IC90, 7.57 and 2.96 µg/mL, respectively.