فهرست مطالب razieh sabet

Thalassemia is a genetic disease that significantly affects human health. The common treatment of thalassemia is the regular injection of red blood cell, which is associated with the accumulation of iron in different tissues of the body, and makes chelation therapy necessary. Deferiprone and deferoxamine are broadly used as iron chelating agents in the vast majority of thalassemia cases. In this study, an efficient method for the synthesis of deferiprone was used by reacting maltol with methylamine in a mixture of water and ethanol as solvent. The structure of deferiprone was assigned using different spectroscopic techniques such as IR, 1H-NMR, and 13C-NMR. The advantages of this pathway are simple, practical, one-pot cascade, mild condition and high yield. The statistics of the Ministry of Health of Iran show the growing trend of deferiprone drug consumption in the country. Therefore, the domestic preparation of this drug can help the pharmaceutical industry in order to reduce costs and make it available for target patients.Keywords: Synthesis, Deferiprone, Maltol, Methylamine, Iron chelating agent.

Hydrogels have unique properties such as water retainer, softness, flexibility, and biocompatibility that cause their application in biology. Among the various hydrogel structures can be referred to intelligent hydrogels. These structures can respond to environmental stimuli. Environmental stimuli can be physical, including temperature or chemicals, such as pH. In this study, the application of smart hydrogels in the fields of medicine, protein, and gene delivery, as well as tissue engineering has been divided and the results of this study show that different types of smart hydrogels with different capabilities have been identified. The mechanical strength of hydrogels is suitable for physiological function and various purposes such as biomedical applications, tendon and ligament repair, cartilage replacement, and tissue engineering. Currently, hydrogels are used to make contact lenses, health products, tissue engineering scaffolds, drug delivery systems, and wound dressing. Most studies in the field of smart drug delivery have been reported, especially in anticancer drugs, and also tissue engineering that can achieve more desirable results in the near future.

Despite extensive research on antimicrobial drugs, efforts to find suitable alternatives to older drugs have not been very successful yet, due to microbial resistance. Heterocycles including azole and pyrimidine derivatives were used to design antimicrobial activity in this research, 12 novel pyrimidine-azole derivatives (3a-3l) that were previously synthesized were screened for their antibacterial and antifungal activities by using CLSI standard method. In this study, we used four species of bacteria, seven species of fungi, and five species of yeast. Molecular docking studies were also performed to investigate their binding mode and orientation toward lanosterol 14-α- demethylase (CYP51), as a plausible mechanism of azole antifungal compounds. The biological results showed that none of the compounds had antibacterial and antifungal effects compared to the control drugs. The molecular docking study showed that the compounds had a low binding affinity in the active site of the lanosterol 14-α- demethylase target, which confirmed the weak antifungal and antibacterial activities of these compounds.

In order to investigate the effects of new drugs, we decided to investigate twelve new derivatives with the basic structure of spirooxindoles that were previously synthesized for antimicrobial, antifungal and anticancer properties.

In this experimental study, we evaluated 12 spirooxyindole derivatives. The inhibitory effect of the compounds has been studied using broth microdilution method based on CLSI protocols on 16 different species of bacteria and fungi. Then, 6 compounds have been selected and their cytotoxicity effects on 2 cell lines MCF-7 and A-549 compared to doxorubicin have been investigated by MTT method. Excel 2013 software was used to perform statistical calculations of the results obtained from each experiment, and GraphPad Curve Expert 1.4 software was used to draw graphs and determine IC50 with a significance level of 0.05.

At the concentration range of 1-512 μg/ml, the synthesized derivatives were not able to inhibit the growth or death of the investigated fungi and bacteria. Only the compound I12 at a concentration of 1000 μg/ml was able inhibit the growth of MFC-7 cell line by 49.23%.

Due to the lack of effective effect of these compounds in inhibiting the growth of bacteria and fungi, for the optimal use of these compounds in the treatment of fungal and bacterial infections, it is necessary to make more changes on their structures. Cytotoxicity assay reveals that the presence of the bulky ester in the N position of the isatin ring as well as the CN attached to the pyridine ring has been beneficial in the effectiveness of these derivatives.

Quantitative structure activity relationships (QSAR) studies, as one of the most important areas in chemometrics, play a fundamental role in predicting the biological activity of new compounds and identifying ligand-receptor interactions. Quantitative relationships between molecular structure and methionine aminopeptidase-2 inhibitory activity of a series of anthranilic acid sulfonamides derivatives were discovered by different chemometrics tools including factor analysis based multiple linear regressions (FA-MLR), principale component regression analysis (PCRA) and genetic algorithm-partial least squares GA-PLS. The FA-MLR describes the effect of geometrical and quantum indices on enzyme inhibition activity of the studied molecules. The quality of PCRA equation is better than those derived from FA-MLR. GA-PLS analysis indicated that the topological (IC4 and MPC06), constitutional (nf) and geometrical (G (N..S)) parameters were the most significant parameters on methionine aminopeptidase-2 inhibitory activity. A comparison between the different statistical methods employed revealed that GA-PLS represented superior results and it could explain and predict 85% and 77% of variances in the pIC50 data, respectively.

Synthesis and investigation of pharmacological activity of novel compounds are time and money-consuming. However, computational techniques, docking, and in silico studies have facilitated drug discovery research to design pharmacologically effective compounds.

Experimental approach:

In this study, a series of quinazoline derivatives were applied to quantitative structure-activity relationship (QSAR) analysis. A collection of chemometric methods were conducted to provide relations between structural features and cytotoxic activity of a variety of quinazoline derivatives against breast cancer cell line. An in silico-screening was accomplished and new impressive lead compounds were designed to target the epidermal growth factor receptor (EGFR)-active site based on a new structural pattern. Molecular docking was performed to delve into the interactions, free binding energy, and molecular binding mode of the compounds against the EGFR target.

A comparison between different methods significantly indicated that genetic algorithm-partial least-squares were selected as the best model for quinazoline derivatives. In the current study, constitutional, functional, chemical, resource description framework, 2D autocorrelation, and charge descriptors were considered as significant parameters for the prediction of anticancer activity of quinazoline derivatives. In silico screening was employed to discover new compounds with good potential as anticancer agents and suggested to be synthesized. Also, the binding energy of docking simulation showed desired correlation with QSAR and experimental data.

Conclusion and implications:

 The results showed good accordance between binding energy and QSAR results. Compounds Q1</sub>-Q30 </sub>are desired to be synthesized and applied to in vitro evaluation.

The extensive use of antifungal drugs and their resistance against fungal infections have led to develop novel antimicrobial compounds. In this research, 14 new pyranopyrazole compounds (D1-D14) which were synthesized before, screened for antimicrobial activity. These compounds consist of a pyranopyrazole scaffold with a phenyl substitution at the 4-position of the pyran ring. Antimicrobial evaluation of the above compounds were investigated against different species of fungi, gram positive and gram negative bacteria by broth micro dilution methods as recommended by CLSI. The specific binding mode or the binding orientation of the compounds to CYP51 active site, have been also performed by molecular modeling investigations. Our results implies that some of our compounds possess desirable inhibitory activity against the tested microorganisms. Our docking study results also showed that the binding free energy values of the compounds are in agreement with the corresponding experimental activity values. By comparison the relationship between chemical structures and biological activities revealed that the presence of a withdrawing substituent at4-position of phenyl group at para position of the pyran ring enhance the antimicrobial activity.

Recently the quinazoline derivatives have attracted much attention for their anticancer properties. In this study a series of new brominated quinazoline derivatives (1a-1g) were synthesized in two steps. In the first step we used N-bromosuccinimide to brominate the anthranilamid. Then in the second step we closed the quinazoline ring by different aromatic aldehydes. Our aldehydes contain different electron donating or electron withdrawing groups at different positions of the aromatic ring. The chemical structures of products were confirmed by spectroscopic methods such as IR, 1HNMR, 13CNMR, and mass spectroscopy. The cytotoxic activities of the compounds were assessed on three cancerous cell lines including MCF-7, A549, and SKOV3 using colorimetric MTT cytotoxic assay in comparison with cisplatin as a standard drug. Our results collectively indicated that 1f and 1g, exhibited the best anti-proliferative activities on three investigated cancerous cell lines.

A facile synthesis of eighteen’s novel derivatives of spiro[indole-thiazolidine]diones (5a-5r) has been developed via hitherto unknown schiff bases. In the first step, we alkylated the isatin ring using different alkyl halides in DMF and in the presence of potassium carbonate and tert-butyl ammonium bromide to get 1a-1i. In the second step, N-substituted isatin (1a-1i) reacted with different amine compounds (2a-2f) to get schiff base intermediates (3a-3r). In the third step, cyclocondensation reaction with mercaptoacetic acid afforded a new class of spiro diones. The amine moieties which are used in the second step of this synthesis are varied from aniline derivatives (2a-2d), phenylpyrazole (2e) and oxazole (2f) analogues. Of the 18 final new compounds 9 analogues derived from aniline, 2 analogues derived from oxazole and 7 of them synthesized from phenylpyrazole analogues. Chemical structures of all new compounds were confirmed by spectroscopic methods such as IR, HNMR and CNMR.