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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Iranian Journal of Pharmaceutical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Antitumor,Imidazoecarboxamide,Potato disc
- چکیده:
- چکیده انگلیسی: In view of potential biological activities of small molecule polyamides, we synthesized some novel N-(2-aminoethyl)-1-benzyl-2- (alkylthio)-1H-imidazole-5-carboxamide (7a,b), and N-(2-(1-benzyl-2-(alkylthio) -1H-imidazole- 5-carboxamido) ethyl)-1-benzyl-2- (alkylthio)-1H-imidazole-5-carboxamides (8a,b) as antitumor agents. The antitumor activity of compounds 7a,b and 8a,b was studied at concentrations of 0.01, 0.1 and 1 mg/ml, using the potato disk bioassay technique. Vincristine at 0.25 mg/ml employed as positive control and had -67.24% tumor inhibition. Maximum % inhibition for potato tumors was found to be -75.52 for 7b at 1 mg/ml.
- انتشار مقاله: 11-04-1386
- نویسندگان: Farzin Hadizadeh,Mohammad Ramezani,Zahra Tayarani,Maryam Eghbal
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Apoptosis,anticancer activity,Quinoline,Resistant cancer cells,Tubulin inhibitors
- چکیده:
- چکیده انگلیسی: Objective(s): Microtubules have key roles in essential cellular processes such as mitosis, cell motion, and intracellular organelle transport. Increasing interest has been given to tubulin binding compounds after the introduction of taxanes into clinical oncology. The object of this study was synthesis and biological evaluation of novel 5,6,7-trimethoxy quinolines as tubulin inhibitors.
Materials and Methods: The cytotoxicity of the newly synthesized compounds was assessed against different human cancer cell lines including MCF-7, A2780, MCF-7/MX, A2780/RCIS, and normal cells. Compounds demonstrating the most antiproliferative activity, were chosen to examine their tubulin inhibition activity and their ability to arrest the cell cycle and induce apoptosis. Molecular docking studies and molecular dynamics simulation of compound 7e in the catalytic site of tubulin were performed.
Results: Most of the synthesized quinolines showed moderate to significant cytotoxic activity against human cancer cells. Compounds 7e and 7f, possessing N-(4-benzoyl phenyl) and N-(4-phenoxy phenyl), respectively, exhibited the most antiproliferative activity more potent than the other compounds and exhibited similar antiproliferative activity on both resistant and parental cancer cells.
Conclusion: Flow cytometry analysis of A2780, A2780/RCIS, MCF-7, and MCF-7/MX cancer cells treated with 7e and 7f exhibited that these compounds arrested the cell cycle (at the G2/M phase) and induced cellular apoptosis in A2780 cancer cells. These quinolines inhibited tubulin polymerization in a way resembling that of CA-4. Molecular dynamics simulation and molecular docking studies of compound 7e into the binding site of tubulin displayed the probable interactions of 7e with the binding site of tubulin.- انتشار مقاله: 30-06-1398
- نویسندگان: Salimeh Mirzaei,Farhad Eisvand,Farzin Hadizadeh,Fatemeh Mosafa,Razieh Ghodsi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: IBD,4-aminosalicylic acid,Azo linkage,PEGylated prodrug,Prodrug
- چکیده:
- چکیده انگلیسی: Objective(s): 4-aminosalicylic acid (4-ASA) is an isomer of mesalazine that has recently been shown to be effective against inflammatory bowel disease (IBD), and more specifically, ulcerative colitis. However, the majority of orally administered 4-ASA is readily and extensively absorbed from the stomach and small intestine, so only a small amount is transported to the colon. A mutual ester and azo prodrug of 4-ASA was synthesized with polyethylene glycol (PEG) and dimethylaniline, respectively , to overcome this issue.
Materials and Methods: The 4-ASA prodrug was synthesized via a two-step process and then characterized by 1H-NMR. The stability of the prodrug was evaluated in simulated gastric fluid (pH 1.2). Furthermore, the in vitro release profiles of the drug conjugate was evaluated at pH 1.2, as well as pH 6.8 in the absence or presence of rat cecal content.
Results: The prepared prodrug was stable at pH 1.2, indicating that it could be protected from the acidic environment of the stomach. Also, the results of drug release at pH 6.8 showed that the amount of 4-ASA released was 63% within 12 hr in the absence of rat cecal content, while in the presence of rat cecal content, 97% of 4-ASA was released from the prodrug in 6 hr.
Conclusion: Overall, the synthesized PEGylated azo-based 4-ASA prodrug could be a potential candidate for targeted drug delivery to the inflamed gut tissue in IBD.- انتشار مقاله: 27-03-1398
- نویسندگان: Fatemeh Sadeghi,Atie Eidizade,Farinaz Saremnejad,Farzin Hadizadeh,Elham Khodaverdi,Abbas Akhgari
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Apoptosis,anticancer activity,Quinoline,Resistant cancer cells,Tubulin inhibitors
- چکیده:
- چکیده انگلیسی: Objective(s): Microtubules have key roles in essential cellular processes such as mitosis, cell motion, and intracellular organelle transport. Increasing interest has been given to tubulin binding compounds after the introduction of taxanes into clinical oncology. The object of this study was synthesis and biological evaluation of novel 5,6,7-trimethoxy quinolines as tubulin inhibitors.
Materials and Methods: The cytotoxicity of the newly synthesized compounds was assessed against different human cancer cell lines including MCF-7, A2780, MCF-7/MX, A2780/RCIS, and normal cells. Compounds demonstrating the most antiproliferative activity, were chosen to examine their tubulin inhibition activity and their ability to arrest the cell cycle and induce apoptosis. Molecular docking studies and molecular dynamics simulation of compound 7e in the catalytic site of tubulin were performed.
Results: Most of the synthesized quinolines showed moderate to significant cytotoxic activity against human cancer cells. Compounds 7e and 7f, possessing N-(4-benzoyl phenyl) and N-(4-phenoxy phenyl), respectively, exhibited the most antiproliferative activity more potent than the other compounds and exhibited similar antiproliferative activity on both resistant and parental cancer cells.
Conclusion: Flow cytometry analysis of A2780, A2780/RCIS, MCF-7, and MCF-7/MX cancer cells treated with 7e and 7f exhibited that these compounds arrested the cell cycle (at the G2/M phase) and induced cellular apoptosis in A2780 cancer cells. These quinolines inhibited tubulin polymerization in a way resembling that of CA-4. Molecular dynamics simulation and molecular docking studies of compound 7e into the binding site of tubulin displayed the probable interactions of 7e with the binding site of tubulin.- انتشار مقاله: 30-06-1398
- نویسندگان: Salimeh Mirzaei,Farhad Eisvand,Farzin Hadizadeh,Fatemeh Mosafa,Razieh Ghodsi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: IBD,4-aminosalicylic acid,Azo linkage,PEGylated prodrug,Prodrug
- چکیده:
- چکیده انگلیسی: Objective(s): 4-aminosalicylic acid (4-ASA) is an isomer of mesalazine that has recently been shown to be effective against inflammatory bowel disease (IBD), and more specifically, ulcerative colitis. However, the majority of orally administered 4-ASA is readily and extensively absorbed from the stomach and small intestine, so only a small amount is transported to the colon. A mutual ester and azo prodrug of 4-ASA was synthesized with polyethylene glycol (PEG) and dimethylaniline, respectively , to overcome this issue.
Materials and Methods: The 4-ASA prodrug was synthesized via a two-step process and then characterized by 1H-NMR. The stability of the prodrug was evaluated in simulated gastric fluid (pH 1.2). Furthermore, the in vitro release profiles of the drug conjugate was evaluated at pH 1.2, as well as pH 6.8 in the absence or presence of rat cecal content.
Results: The prepared prodrug was stable at pH 1.2, indicating that it could be protected from the acidic environment of the stomach. Also, the results of drug release at pH 6.8 showed that the amount of 4-ASA released was 63% within 12 hr in the absence of rat cecal content, while in the presence of rat cecal content, 97% of 4-ASA was released from the prodrug in 6 hr.
Conclusion: Overall, the synthesized PEGylated azo-based 4-ASA prodrug could be a potential candidate for targeted drug delivery to the inflamed gut tissue in IBD.- انتشار مقاله: 27-03-1398
- نویسندگان: Fatemeh Sadeghi,Atie Eidizade,Farinaz Saremnejad,Farzin Hadizadeh,Elham Khodaverdi,Abbas Akhgari
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: vitamin B12,Striatum,Cerebral cortex Methamphetamine Neurotoxicity
- چکیده:
- چکیده انگلیسی: Objective(s): Methamphetamine (METH) is a powerful stimulant drug that directly affects the brain and induces neurological deficits. B12 is a water-soluble vitamin (vit) that is reported to attenuate neuronal degeneration. The goal of the present study is to investigate the effect of vitamin B12 on METH’s neurodegenerative changes.
Materials and Methods: Two groups of 6 animals received METH (10 mg/kg, interaperitoneally (IP)) four times with a 2 hr interval. Thirty mins before METH administration, vit B12 (1 mg/kg) or normal saline were injected IP. Animals were sacrificed 3 days after the last administration. Caspase proteins levels were measured by Western blotting. Also, samples were examined by TUNEL assay to detect the presence of DNA fragmentation. Reduced glutathione (GSH) was also determined by the Ellman method.
Results: The pathological findings showed that vit B12 attenuates the gliosis induced by METH. Vit B12 administration also significantly decreased the apoptotic index in the striatum and the cerebral cortex (P<0.001). It also reduced caspase markers compared to the control (PConclusion: The current study suggests that parenteral vit B12 at safe doses may be a promising treatment for METH-induced brain damage via inhibition of neuron apoptosis and increasing the reduced GSH level. Research focusing on the mechanisms involved in the protective responses of vit B12 can be helpful in providing a novel therapeutic agent against METH-induced neurotoxicity.- انتشار مقاله: 15-02-1396
- نویسندگان: Mohamad Moshiri,Seyed Mojtaba Hosseiniyan,Seyed Adel Moallem,Farzin Hadizadeh,Amir Hosein Jafarian,Ameneh Ghadiri,Toktam Hoseini,Mahmoud Seifi,Leila Etemad
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Molecular docking,Synthesis,p-glycoprotein,Quinoline,P-gp inhibition
- چکیده:
- چکیده انگلیسی: Objective(s): In the present study,a new series of 6-methoxy-2-arylquinoline analogues was designed and synthesized as P-glycoprotein (P-gp) inhibitors using quinine and flavones as the lead compounds.
Materials and Methods: The cytotoxic activity of the synthesized compounds was evaluated against two human cancer cell lines including EPG85-257RDB, multidrug-resistant gastric carcinoma cells (P-gp-positive gastric carcinoma cell line), and EPG85-257P, drug-sensitive gastric carcinoma cells. Compounds showing low to moderate toxicity in the MTT test were selected to investigate their P-gp inhibition activity. Moreover, trying to explain the results of biological experiments, docking studies of the selected compounds into the homology-modeled human P-gp, were carried out. The physicochemical and ADME properties of the compounds as drug candidate were also predicted.
Results: Most of our compounds exhibited negligible or much lower cytotoxic effect in both cancer cells. Among the series, 5a and 5b, alcoholic quinoline derivatives were found to inhibit the efflux of rhodamine 123 at the concentration of 10 μM significantly.
Conclusion: Among the tested quinolines, 5a and 5b showed the most potent P-gp inhibitory activity in the series and were 1.3-fold and 2.1-fold stronger than verapamil, respectively. SAR data revealed that hydroxyl methyl in position 4 of quinolines has a key role in P-gp efflux inhibition of our compounds. ADME studies suggested that all of the compounds included in this study may have a good human intestinal absorption.- انتشار مقاله: 01-04-1396
- نویسندگان: Sayyed Mohammad Abutorabzadeh,Fatemeh Mosafa,Farzin Hadizadeh,Razieh Ghodsi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: antidote,acute toxicity,Intravenous lipid emulsion Methamphetamine
- چکیده:
- چکیده انگلیسی: Objective(s): The increasing use of methamphetamine (METH) in the last decades has made it the second most abused drug. Advancs in the area of intravenous lipid emulsion (ILE) have led to its potential application in the treatment of poisoning. The present study aims to investigate the potential role of ILE as an antidote for acute METH poisoning.
Materials and Methods: Two groups of six male rats were treated by METH (45 mg/kg), intraperitoneally. Five to seven min later, they received an infusion of 18.6 ml/kg ILE 20% through the tail vein or normal saline (NS). Locomotor and behavioral activity was assessed at different time after METH administration. Body temperature and survival rates were also evaluated. Brain and internal organs were then removed for histological examination and TUNEL assay.
Results: ILE therapy for METH poisoning in rats could prevent rats mortalities and returned the METH-induced hyperthermia to normal rates (P<0.05). ILE reduced freezing and stereotyped behaviors and increased rearing responses (P<0.05). Locomotor activity also returned to control levels especially during the last hours of the experiment. ILE administration decreased the prevalence of pulmonary emphysema in the lungs (PP<0.01) and percentages of TUNEL positive cells in the brain (P<0.05), in comparison with the control group.
Conclusion: ILE could reduce the severity of METH- induced toxicity as well as mortality rate in the animals. Intravenous infusion of lipid emulsion may save the life of patients with acute METH intoxication who do not respond to standard initial therapy.- انتشار مقاله: 12-11-1395
- نویسندگان: Ameneh Ghadiri,Leila Etemad,Mohammad Moshiri,Seyed Adel Moallem,Amir Hossein Jafarian,Farzin Hadizadeh,Mahmoud Seifi
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Zeolite,Indomethacin,Ibuprofen,Controlled drug delivery-systems
- چکیده:
- چکیده انگلیسی: Objective(s): In this research, zeolite X and zeolite Y were used as vehicle to prepare intestine targeted oral delivery systems of indomethacin and ibuprofen.
Materials and Methods: A soaking procedure was implemented to encapsulate indomethacin or ibuprofen within synthetic zeolites. Gravimetric methods and IR spectra of prepared formulations were used to assess drug loading efficiencies into zeolite structures. Scanning Electron Microscopy (SEM) was also utilized to determine morphologies changes in synthetic zeolites after drug loading. At the next stage, dissolution studies were used to predict the in vivo performance of prepared formulations at HCl 0.1 N and PBS pH 6.5 as simulated gastric fluid (SGF) and simulated intestine fluid (SIF), respectively.
Results: Drug loadings of prepared formulations was determined between 24-26 % w/w. Dissolution tests at SGF were shown that zeolites could retain acidic model drugs in their porous structures and can be able to limit their release into the stomach. On the other hand, all prepared formulations completely released model drugs during 3 hr in simulated intestine fluid.
Conclusion: Obtained results indicated zeolites could potentially be able to release indomethacin and ibuprofen in a sustained and controlled manner and reduced adverse effects commonly accompanying oral administrations of NSAIDs.- انتشار مقاله: 30-02-1393
- نویسندگان: Elham Khodaverdi,Reza Honarmandi,Mona Alibolandi,Roxana Rafatpanah Baygi,Farzin Hadizadeh,Gholamhossein Zohuri
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Inhibitors,p38 MAP kinase,Pyridinylimidazoles
- چکیده:
- چکیده انگلیسی: Objective(s)
Inhibitors of p38 MAP kinase are considered as suitable target in the treatment of inflammatory diseases such as rheumatoid arthritis and bowel inflammatory diseases. The development of 5-alkylthio-1-aryl-2-(4-pyridinyl) triazoles as inhibitors of p38 MAP kinase is described. These are analogues of 4- pyridinyl imidazole p38 MAP kinase inhibitor reported by Merck Research Laboratories, in which imidazole ring has been replaced with triazole.
Materials and Methods
Reaction of pyridine-4-carboxylic acid hydrazide 1 and arylisothiocyanate (2a, b) gave the intermediate thiourea derivative 3a, b (Figure 2). Refluxing of the latter in aqueous saturated sodium carbonate gave 1-aryl-5-mercapto-2-(4-pyridinyl) triazoles 4a, b. Treatment of 4a, b with alkyl iodide afforded the desired 5-alkylthio-1-aryl-2-(4-pyridinyl) triazoles (5a-d). P38 MAP kinase inhibitory activity of the synthesized compounds was evaluated in vitro by ELISA method and also by molecular docking.
Results
Compound 5c at 1 µM concentration and compound 5d at 1 µM and 10 µM significantly inhibited the p38 phosphorylation. These inhibitory effects are equal to those of standard compound SB202190 and no significant differences were observed.
Conclusion
We demonstrated that both tested compounds have inhibitory effect on p38 MAP kinase and we did not find significant difference between their inhibitory effects and those of standard inhibitor SB202190.- انتشار مقاله: 25-06-1394
- نویسندگان: Seyed Adel Moallem,Farzin Hadizadeh,Fatemeh Abdol Abadi,Mahmoud Shahraki,Jamal Shamsara
- مشاهده