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Home > The Solution Properties of Amphiphilic Drugs and Their Interactions With Surfactants and Human Serum Albumin

The Solution Properties of Amphiphilic Drugs and Their Interactions With Surfactants and Human Serum Albumin

Thesis Info

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Author

Usman, Muhammad

Program

PhD

Institute

Quaid-I-Azam University

City

Islamabad

Province

Islamabad.

Country

Pakistan

Thesis Completing Year

2011

Thesis Completion Status

Completed

Subject

Chemistry

Language

English

Link

http://prr.hec.gov.pk/jspui/handle/123456789/1774

Added

2021-02-17 19:49:13

Modified

2024-03-24 20:25:49

ARI ID

1676727596774

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This dissertation reports physicochemical behaviour of some amphiphilic drugs as well as their interaction with anionogenic tensides (ionic surfactants) and Human serum albumin (HSA). A detail study of self aggregation of these drugs i.e. Clindamycine Phosphate (CLN), Quinacrine 2HCl (QUN), Chloroquine diphosphate (CLQ), Dexamethasone Sodium Phosphate (DSP) , Pefloxacin Mesylate (PFL), Citalopram HBr (CIT), Fluphenazine 2HCl (FLP), Trifluperazine 2HCl (TRF) and Certizine 2HCl (CRT) has been worked out. Surface tension and specific conductivity were measured to calculate the critical micelle concentration (CMC) of drugs and in this way their surface and thermodynamic parameters have been estimated. Surface activity was studied by measuring surface parameters i.e. surface pressure, Л, surface excess concentration, Г, area per molecule of ° drug and standard Gibbs free energy of adsorption, DGads . The electrical conductivity was measured as a function of concentration in the temperature range of 293-323K and CMC was determined. Consequently ° thermodynamic parameters like standard free energy of micellization, DGm , standard ° ° enthalpy of micellization, DH m and standard entropy of micellization, DS m were computed using closed association model. Aggregation properties of some structurally related drugs trifluperazine and fluphenazine and Quinacrine and Chloroquine have also been brought under study. For the most of drugs, association was found to be both enthalpy as well as entropy driven. Dexamethasone sodium phosphate, however, undergoes open association rather than micellization. We have also studied interaction of amphiphilic drugs with anionic surfactants sodium dodecyl sulfate (SDS) and cationic surfactant cetyltrimethyl ammonium bromide (CTAB). Aqueous micellar solutions of these surfactants were used for solublization of these drugs. The change of CMC of surfactant due to drug was determined by UV/Visible spectroscopy and conductivity method. UV/Visible spectroscopy was used to check the qualitative and quantitative features of this interaction and to calculate partition coefficient (Kx), free energy of partition and number of drug molecules per micelle while conductivity method is helpful to calculate different thermodynamic parameters. The complexation of amphiphilic drugs with HSA at physiological conditions (pH 3.0 and 7.4) have also been analyzed by using UV/Visible spectroscopy, fluorescence spectroscopy and dynamic laser light scattering. In this way values of drug-protein binding constant, number of binding sites and hydrodynamic radii were calculated and discussed in detail.
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Salicylic and Abscisic Acid Induced Physiological and Biochemical Changes in Selected Wheat Cultivars under Heat Stress

High temperature is a crucial abiotic stress which limits yield in crop plant especially in wheat (Triticum aestivum) at post anthesis stages. Salicylic acid (SA) and abscisic acid (ABA) are the plant growth hormones which act as signaling molecules and confer stress tolerance in crop plants. Five wheat cultivars namely Pakistan-2013, NARC-2009, GA-02, Inqalab-91 and BAJ were assessed under heat stress by applying SA and ABA through seed priming and foliar application under field and in-vitro conditions. Effect of terminal heat stress on wheat was evaluated in filed by normal and late sowing. Normal sown crop escaped the terminal heat stress; while in late sowing, terminal heat stress negatively affected yield related traits and reduced yield by 25%, SA and ABA seed priming improved the grain yield 17% and 13% respectively. During in-vitro evaluation, exogenous SA and ABA application reduced the effects of heat stress, seed primed plants of both the hormones showed 13% and 15% higher yields under heat stress than the control. Heat stress affected physiological traits and reduced cell membrane stability, leaf relative water content, and total chlorophyll content. Foliar application of SA enhanced membrane stability, leaf relative water content and chlorophyll content by 32, 23 and 22% respectively and reduced the electrolyte leakage by 16%. Among the biochemical traits accumulation of soluble sugars, protein, proline content, hydrogen peroxide content and malondialdehyde content in the cells was increased, and antioxidant enzymatic activities were up-regulated under heat stress. Further 37, 74 and 87% elevated soluble protein, proline and soluble sugar content was observed in response to SA foliar. SA foliar application reduced hydrogen peroxide content and malondialdehyde content by 42 and 39% respectively. xxii Superoxide dismutase, peroxidase, ascorbate peroxidase and catalase activity was doubled under heat stress in response to SA and ABA seed priming as compared to control. Protein profiling and expression analysis was carried out for NAC transcription factors in response to heat stress and hormonal application. Several different heat shock proteins ranging from 50 to 98 kDa were produced under heat stress and in response to hormonal application in all selected cultivars. A novel heat shock protein of 60 kDa was expressed in NARC-2009 in response to salicylic acid seed priming whose sequence analysis identified it as a chaperone protein, RuBisCO large subunit-binding protein subunit alpha and beta (CPN-60 α and β). NAC transcription factors showed varied response to heat stress and hormonal application in all cultivars. Transcript level of TaNAC6B was higher under salicylic acid application in heat stress, and TaNAC67 was up-regulated by both salicylic and abscisic acid application during heat stress. TaNAC2D was up-regulated in NARC-2009 by salicylic and abscisic acid seed priming and by SA foliar application in GA-02. TaNAC6B, TaNAC67 and TaNAC2B showed higher transcript level in BAJ under all hormonal applications under heat stress. The expression of NAC transcriptional factors in response to salicylic acid and abscisic acid priming confirmed the positive role of these two hormones in enhancing tolerance against heat stress in tested wheat varieties including BAJ. These findings may be used to screen wheat cultivars through expression analysis against heat stress, develop heat tolerant cultivars and to improve performance of existing wheat cultivar against heat stress through hormonal priming.