The thermodynamic dissociation constants of the anticancer drugs camptothecine, 7-ethyl-10-hydroxycamptothecine, 10-hydroxycamptothecine and 7-ethylcamptothecine by the least-squares nonlinear regression of multiwavelength spectrophotometric pH-titration data

publication · 7 years ago
by Milan Meloun, Sylva Bordovska, Ales Vrana (University of Pardubice)
MarvinView Calculator Plugins (logP logD pKa etc...)
The mixed dissociation constants of four anticancer drugs – camptothecine, 7-ethyl-10-hydroxycamptothecine, 10-hydroxycamptothecine and 7-ethylcamptothecine, including diprotic and triprotic molecules at various ionic strengths I of range 0.01 and 0.4, and at temperatures of 25 and 37 °C – were determined with the use of two different multiwavelength and multivariate treatments of spectral data, SPECFIT32 and SQUAD(84) nonlinear regression analyses and INDICES factor analysis. A proposed strategy for dissociation constants determination is presented on the acid–base equilibria of camptothecine. Indices of precise modifications of the factor analysis in the program INDICES predict the correct number of components, and even the presence of minor ones, when the data quality is high and the instrumental error is known. The thermodynamic dissociation constant image was estimated by nonlinear regression of {pKa, I} data at 25 and 37 °C: for camptothecine image and 3.02(8), image and 10.23(8); for 7-ethyl-10-hydroxycamptothecine, image and 2.46(6), image and 8.74(3), image and 9.47(8); for 10-hydroxycamptothecine image and 2.84(5), image and 8.92(2), image and 9.98(4); and for 7-ethylcamptothecine image and 3.30(16), image and 10.98(18). Goodness-of-fit tests for various regression diagnostics enabled the reliability of the parameter estimates found to be proven. Pallas and Marvin predict pKa being based on the structural formulae of drug compounds in agreement with the experimental value.
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