Antifungal activities, QSAR

A fundamental difference between 3D- and a 2D-QSAR equation is the non-existence of conformational dependent secondary sites in the latter. Hence, a direct transposition of 3D- and 2D-models is not always possible but the global properties of the chemical structures, if relevant to the activity, may show their presence in both of them. Moreover, in a broader perspective, all 2D-QSAR parameters—physicochemical as well as structural—can be considered as one or the other form of global descriptors. In light of this, to bridge the 2D- and 3D-features the following 2D-QSAR equations have been derived for the antifungal activity of 2,3,4-substituted thiazolidines (Table 21). 

These compoimds have been tested in vivo against wheat leaf rust, Puc-cinia recondite, at a fixed dose of 0.001 M. The following equation represents the best QSAR model for the antifungal activity (D = log[a/(100 - a)] - log Mw where, a is the percentage inhibition and Mw is the molecular weight of the tested compound) of these compoimds. 

On the basis of this equation Zou et al. have concluded that hydrophobic compounds with inductively electron-donating ortho substituents would be favorable for the activity [193]. In continuation of this, Zou and coworkers have carried out CoMFA-based 3D-QSAR analysis of these compounds together with 5-[l-aryl-l,4-dihydro-6-methylpyridazin-4-one-3-ylj-2-arylamino- 1,3,4-oxadiazoles [ 194]. Here also the antifungal activity of these compounds has been found to be well explained by their steric and electrostatic properties. In addition to this, it has confirmed the bioisosterism... 

Ursu, O., Costescu, A., Diudea, M.V. and Parv, B. (2004) QSARs of some novel isosteric heterocyclic with antifungal activity. Carpathian J. Math., 20, 267-274. 

In this review we have discussed published results concerning the QSAR research on antimicrobial properties of synthetic and natural compounds. Antifungal and antimicrobial activity of some coumarin derivatives, various types of biological activities of benzamides, several studies on cinnamic acid derivatives with antibacterial and antifungal activity, reports on the biological activity of homoisoflavanones and phenolic compounds, as well as pharmaceutical applications of furan derivatives have been shown. 

Gonzdlez-Diaz, H., Prado-Prado, F. J., Santana, L., Uriarte, E. (2006). Unify QSAR approach to antimicrobials. Part 1 predicting antifungal activity against different species. Bioorganic Medicinal Chemistry, 14, 5973. 

Lewis, D. F. V., Wiseman, A., and Tarbit, M. H. (1999) Molecular modeling of lanosterol 14-alpha-demethylase (CYP51) from Saccharomyces cerevisiae via homology with CYP102, a unique bacterial cytochrome P450 isoform quantitative structure-activity relationships (QSARs) within two related series of antifungal azole derivatives../. Enz. Inhib. 14, 175-192. 

Talele, T. T. and Kulkami, V. M. (1999) Three-dimensional quantitative structure-activity relationship (QSAR) and receptor mapping of cytochrome P-450(14 alpha DM) inhibiting azole antifungal agents.. /. Chem. Inf. Comput. Sci. 39, 204-210. 

Although not perfect, Hansch s lipophilicity parameter and log P values are the most widely used parameters in QSAR studies. In addition to their effectiveness in predicting biological activity through target binding (pharmacodynamics), both parameters also affect pharmacokinetics. The pharmacokinetic applications of log P and 7r-values can be seen in Lipinski s rules and a Case Study (Carboxylate Antifungals) later in this chapter. 

Di Santo R, Tali A, Costi R, Botta M, Artico M, Corelli F, Forte M, Caporuscio F, Angi-olellaL, PalamaraAT (2005) Antifungal Agents. 11. N-Substituted Derivatives of l-[(Aryl) (4-aryl-lH-pyrrol-3-yl)methyl]-lH-imidazole Synthesis, anti-eandida activity, and QSAR studies. J Med Chem 48 5140-5153... 

Gonz lez-Diaz, H., 8c Prado-Prado, F. (2008). Unified QSAR and network-based computational chemistry approach to antimicrobials, part 1 multispecies activity models for antifungals. Journal of Computational Chemistry, 29, 656. 

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