COMPUTATIONAL AND POLAROGRAPHIC STUDY ON DRUG-RECEPTOR INTERACTION FOR CARVEDILOL

Objective: The aim of this study was to evaluate Carvedilol-receptor binding using computational and polarographic methods.Methods: Differential pulse polarographic (DPP) wave was measured for carvedilol, serine, and aspartic acid in phosphate buffer solution pH 7.4at 37 °C. Interaction of drug receptors with two amino acids serine and aspartic acid was studied by linking the thermodynamic (Keq) and kinetic behavior. The forward reaction rate constant (k1) and reverse reaction rate constant (k-1) was calculated for carvedilol–receptor complexes and through the half-life time was also calculated.Results: The study found that carvedilol, serine and aspartic acid electrical active agents and have E 1/2 0.148, 0.127 and 0.119 V respectively. After formation of drug-receptor molecular complexes, a negative displacement in carvedilol half-wave potential value. Gibbs, free energy was calculated and found to be a negative value for all the molecular complexes indicate that spontaneous interaction occurred. The chemical affinity was also calculated which gave a positive result and indicated a high tendency of molecules to associate with each other. A computational study using the Gaussian software, DFT-6311G on carvedilol-receptor molecular complexes gave significant agreement of complex behavior in the theoretical study with the polarographic study, depending on the values of the energy gap between HOMO-LUMO.Conclusion: the study showed that there is a good rapprochement between theoretical and experimental results allows the possibility of evaluated drug–receptor interaction in Subsequent studies theoretically, also showed the possibility to determine the spontaneously and chemical affinity of drug-receptor molecular complex formation based on polarographic result

DETERMINATION OF PHYSICOCHEMICAL AND GEOMETRICAL PROPERTIES OF SOME CARVEDILOL DEREVITIVES

ABSTRACTObjective: Five derivatives of Carvedilol with different activities were studied in order to suggest unprepared derivative of carvedilol and suggestiona general equation to calculate the activity foe any Carvedilol derivative..Methods: GAUSSIAN 03 software employed to calculate physicochemical and geometrical properties of carvedilol derivatives, the calculated quantumchemical parameters are: The energy gap between the highest occupied molecular orbital and lowest unoccupied molecular orbital (HOMO-LUMO),dipole moment (μ), electronegativity (χ), electron affinity (A), global hardness (η), ionization potential (I), and the global electrophilicity (ω). Theresulting properties used in quantitative structure-activity relationship equation to predict activity.Results: Suggested unprepared carvedilol derivative with an activity of 1.99 × 10 mg as well as development of a general equation, two formula forcalculate activity of carvedilol derivatives specifically Log 1/C = −29.5744 + 17.1334 Log p + 19603.97 ∆ HOMO-LUMO + 2.7725 μ – 38902 η by meanof physicochemical properties and Log 1/C = 2828.25 + 15.01 N electron density − 308.016 O electron density + 306.97 H electron density + 0.32477molecular length by mean of geometrical properties.−5Conclusion: This process may be considered the cost- and time-consuming process, according to the ability of suggestions, new structures to besynthesized using computational chemistry methods.Keywords: Quantitative structure-activity relationship, Density functional theory, Highest occupied molecular orbital and lowest unoccupiedmolecular orbital gap, Global hardness, Global electrophilicity

Anticancer Drug 5-Fluorouracil in Aqueous Solution by Differential Pulse Polarography: An Assessment of Optimum Conditions

The potassium phosphate buffer as a supporting electrolyte of anticancer drug (5-fluorouracil (5-FU)) was the best among solutions of sodium phosphate buffer and Britton Robinson buffer in differential pulse polarography (DPP) at pH = 7.0 and T = 37 ℃. The changes of temperature did not effect on inactivity of the supporting electrolyte (potassium phosphate buffer at T = 10-50 ℃), and pH of the solution did not exceed 2% of each 5 ℃ (at pH = 7.0, by modified thermostat cell). However, the frequency measurements showed clear effect of temperature on diffusion current (IP /μA) of the chemotherapy compound in the range of 20-50 ℃ and under primary conditions. Then, the polarography measurements of 5-FU drug (at 10 μM, pH = 7 and T = 37 ℃) gradually led to the optimum conditions: deposition potential =–0.9 V; drop size = 9.0 mm3; deposition time = 15.0 s; equilibration time = 5.0 s; pulse amplitude = 100 mV; pulse time = 7.0 ms; voltage step = 6 mV; voltage step time = 0.3 s; and sweep rate = 20.0 mV/s. The thermal assessment of 5-FU drug (after achievement of the optimum conditions) in a new thermostat vessel at HMDE by DPP showed that the reaction of 5-FU molecules represented pseudo first order reaction, instead of first order); the secondary waves of 5-FU drug may be due to formation of molecular complexes in aqueous solution and the reduction of 5-FU molecules at mercury surface electrode appeared as physisorption, instead of chemisorption