88 research outputs found
Analyzing the Impact of Imported Plans in Reshaping Iranian Ancient Cities: A Historical Study
Iranian cities which have grown and reached completion (based on national innovation and creativity) all along the history gradually changed over the decades and have lost their physical characteristics as well as their cultural, social, artistic and historical values. Periodical changes began with the conditional revolution and from Boos. By accepting modernism and following the Western model, waster changes were initiated. Urbanism Trend in new period was neither improved based on the Iranian vernacular characteristics, nor by creating proper background of accepting western samples. There were only changes by imitating the West and capitalism, which was influenced by Iranian Sick relations with Western countries. These changes destroyed the old urban fabric and evolutionary in Tehran and other large cities that accepted foreign samples, spreading up in all fields of decentralization. Problems such as high population density, pollution, sprawls, etc., occurred. Findings of this research show that, producing western old-fashioned comprehensive plans couldnât act properly in different planning scales and was not successful in leading cities basically and ordering their development and growth. This present article, based on a historical-interpretative approach, focuses on the roots and causes of Western thoughts, creative processes, and imitations and their symptoms and impacts in Iranian urban development system
Dietary Natural Products as Potential Tumor Chemo-Sensitizers
P-glycoprotein (P-gp) is a membrane ATP-binding transporter that detoxifies cells from different xenobiotics. Multiple drug resistant (MDR) cells can be sensitized toward anticancer agents when treated with P-gp inhibitors/modulators (chemo-sensitizers). Regarding the requirement of high serum concentrations of P-gp inhibitors leading to potential toxicity, dietary phytochemicals are very important and they may interact with co-administered pharmaceuticals as P-gp substrates, leading to altered pharmacokinetics. In silico models for predicting probable binding mode of dietary phytochemicals to P-gp are useful in the early phase of drug discovery projects since they describe structural features in binding to P-gp and hence designing novel anti-MDR scaffolds.
Introduction: As a part of our ongoing studies on virtual analysis of bioactive phytochemicals and to explore new substances that do not exhibit significant toxicity at doses required for P-gp inhibition, we aimed to get more insight into the interactions of P-gp and a few dietary natural constituents as tumor chemosensitizing agents.
Methods and Results: Radiographic 3D holo structure of P-gp was retrieved from protein data bank (4XWK; www.rcsb.org). Lamarckian genetic algorithm of AutoDock 4.2 was used to simulate the binding of dietary compounds. All ab initio studies were done with functional B3LYP associated with split valence basis set using polarization functions (Def2-SVP) by ORCA quantum chemistry package. Our study proposed the dominant role of R-site in binding to Curcuminoids (Curcumin II; -8.17 kcal/mol). In the case of black pepper, hydrophobic contacts seemed to be important in Piperine/P-gp complex. It was also proposed that Piperine carbonyl might be a good mimic of Curcumin II enone group due to the formation of H-bonds (Gln986). Among the catechins of green tea, Epicatechin gallate might not be identified as modulator/substrate since relatively similar ÎGbs were recorded within M, H and R sites. Quercetin was not preferentially docked within H-site (-4.77 kcal/mol) in accordance to the previous reports. Within the H-site, Epigallocatechin (green tea) was the weakest binder (-4.31 kcal/mol) and amino acid decomposition analysis dedicated -2.66 and -8.76 kcal/mol attractive forces for interaction with Glu180 and Lys185, respectively.
Conclusions: Combined molecular docking/quantum mechanical studies revealed that among assessed phytochemicals, Bergapten (grape fruit) might be identified as P-gp modulator. Other constituents exhibited more affinity toward R-site with Curcumionoids being the top-ranked ones. Results indicated Lys185, Glu871 and Glu986 as important interacted residues with Curcuminoids due to strong hydrogen bondings
Green-oriented planning for shrinking cities through an integrated ecosystem services/disservices analysis: A Case of Minoo Island, Iran
Systematic Modeling of Drug P-Glycoprotein Interactions via Combined Docking/QM Approach
Introduction: The overexpression of P-gp in cancer tumor cells results in increased efflux of chemotherapeutic compounds. This phenomenon leads to the wide-spectrum resistance of cancer cells to variant drugs or multi drug resistance (MDR). Regarding the important biological role of P-gp with regard to cancer therapy, in silico analysis of binding affinity/mode of diverse anticancer drugs toward P-gp may be an active area of research since it provides more insight into the binding interactions and key amino acid residues that were involved.
Methods and Results: Ligand-flexible docking studies were performed using the molecular docking software, AutoDock 4.2. To elucidate the interactions of selected anticancer drugs, all the related structures were docked into the active site of validated P-gp target (4XWK). Quantum mechanical calculations were applied to intermolecular binding energy analysis in terms of drug-residue binding interactions via functional B3LYP in association with split valence basis set using polarization functions (Def2-SVP).
Mitomycin was found to be the weakest binder with -7.29 kcal/mol energy. Bisantrene was the top-ranked binder (-10.59 kcal/mol) with H-bond and lipophilic interaction patterns. To explain more, Asn838 participated in bidentate H-bonding with nitrogen atom of imidazole ring. Another H-bond interaction was detected in the case of Ser725 within the same ring but different nitrogen atom of the drug molecule. Besides hydrogen bonding, it was revealed that 12 hydrophobic residues interacted with Bisantrene. Within the evaluated drugs, unlike Epothilone E and F, no H-bonds could be detected for Epothilone A, B, C & D. Such observation was pertained to the presence of hydroxymethyl moiety on the thiazole ring of Epothilone E and F which provided well-oriented H-bonds with Ala307. Despite observed interactive residues, lower binding affinity of Epothilone F persuaded us to run QM job in terms of drug-residue binding interactions. It was interestingly concluded that a few residues made repulsive forces with the drug, a result that might explain lower affinity of this molecule toward P-gp.
Conclusions: Collective in silico exploration of a few anticancer drugs provided some insights into the binding mode toward P-gp as an interfering target in chemotherapeutic strategies. On the basis of obtained results, structure binding relationship pattern for studied anticancer drugs were developed
Response Surface Methodological Approach toward Optimization of a RP-HPLC Method to Determine Paracetamol in Tablets
Response surface methodology (RSM) was applied to develop an RP-HPLC method in which paracetamol was analyzed and determined on a C18 column with UV detection. To explain more, RSM was used to statistically model the impact of flow rate (ml.min-1) (A), column temperature (°C) (B) and mobile phase composition (H2O: MeOH) (C)on the retention time (RT) of Paracetamol within tablets.
Introduction: The major goal of this investigation was to optimize an RP-HPLC method which is simple, linear, accurate, sensitive and selective in determination of Paracetamol in solid dosage forms.
Methods and Results:Three distinctive levels were dedicated to each evaluated factor.Box-Behnken experimental design including seventeen independent runs within a range of 25-50% MeOH ratio (mobile phase), 25-45 ÂșC and 0.7-1.3 mL. min-1 flow rate were carried out to explore the effectivefactors onRT of Paracetamol using RP-HPLC method. ANOVA results revealed that quadratic model was significant (Model F-value of 225.65) and could best describe the relationship between dependent variable (RT) and independent ones:
RT= 3.30 - 1.2A - 0.38B - 0.80C + 0.30AC + 0.43BC + 0.53A2
As can be understood from the model terms, the most significant term was the solvent ratio and all the factor levels were indirectly proportional to the Rt. Moreover, the interaction of column temperature and solvent ration seemed to be more important. It was also predicted that optimum assay condition included 1:2 ratio of methanol to water, column temperature of 35ÂșC and mobile phase flow rate of 1.3 mL.minâ1. Using this optimum condition, baseline separation of the drug was achieved with a good resolution and a run time of 2.1 min. The optimized method was validated in terms of linearity, accuracy, limit of detection and limit of quantification of paracetamol within a few commercially available Paracetamol tablets.
Conclusions:The optimized RP-HPLC technique provided a convenient and efficient method toward qualitative/quantitative analysis of Paracetamol in its tablets. The improved method is also rapid and sensitive enough to be used for single tablet analysis
Investigating the Relationship between the Structure of Educational Program and Research Outputs in Top Iranian and international Architectural Schools
Academic educational programs such as architectural programs are all influenced by the quality of education and Premier academic staff. They also consist of theoretical, practical and experimental units. One of the criteria for evaluating such international educational programs is the rate of their research outputs in an international ranking called QS. The lack of knowledge about the relationship between the structure of educational programs and the rate of their research outputs in an international scale causes the inconsistency between educational programs and research outputs. This matter consequently leads to a lower international ranking of universities. Thus, the current article aimed at addressing this issue for the first time. To collect data, the thirteen and three top international and Iranian architectural faculties with higher impact factors in the global rankings were selected. Then, the meaningful relationship between the research outputs and their educational systems upstream and downstream levels, including the relationship between the quality of education, educational programs, faculty members and allotted hours to theoretical, practical and experimental units and the research outputs were investigated. The results revealed that there is no relationship between having top academic staff and allotted hours to theoretical, practical and experimental units and the research outputs in all top international faculties. In addition, the results showed that there is no relationship between the hours allotted to research units and the research outputs of top three Iranian architectural faculties
Antioxidant properties of hydroxycinnamic acids: a review of structure- activity relationships
Hydroxycinnamic acids (HCAs) are important phytochemicals possessing significant biological properties.
Several investigators have studied in vitro antioxidant activity of HCAs in detail. In this review, we have gathered the
studies focused on the structure-activity relationships (SARs) of these compounds that have used medicinal chemistry to
generate more potent antioxidant molecules. Most of the reports indicated that the presence of an unsaturated bond on the
side chain of HCAs is vital to their activity. The structural features that were reported to be of importance to the antioxidant
activity were categorized as follows: modifications of the aromatic ring, which include alterations in the number and
position of hydroxy groups and insertion of electron donating or withdrawing moieties as well as modifications of the carboxylic
function that include esterification and amidation process. Furthermore, reports that have addressed the influence
of physicochemical properties including redox potential, lipid solubility and dissociation constant on the antioxidant activity
were also summarized. Finally, the pro-oxidant effect of HCAs in some test systems was addressed. Most of the investigations
concluded that the presence of ortho-dihydroxy phenyl group (catechol moiety) is of significant importance to
the antioxidant activity, while, the presence of three hydroxy groups does not necessarily improve the activity. Optimization
of the structure of molecular leads is an important task of modern medicinal chemistry and its accomplishment relies
on the careful assessment of SARs. SAR studies on HCAs can identify the most successful antioxidants that could be useful
for management of oxidative stress-related diseases
Dabco containing acidic poly(ionic liquid): An efficient catalyst for the one-pot Preparation of 2,3-dihydroquinazoline-4(1H)-ones
1,4-Diazabicyclo[2.2.2]octane (DABCO) containing acidic poly(ionic liquid) (DAIL) has been prepared via condensation of 1,4-dichloro butane and DABCO, as an efficient acidic catalyst and has been applied in the one-pot preparation of 2,3-dihydroquinazolin-4(1H)-one derivatives. This catalyst has been characterized by FT-IR and TGA. According to the obtained results including time, yield and recyclability, DAIL could be considered as an efficient catalyst for organic transformations
Antioxidant Properties of Hydroxycinnamic Acids: A Review of Structure- Activity Relationships
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