Hansch Analysis
Hansch analysis is used widely in the field of medicinal chemistry. It is the analysis that investigates the quantitative relationship and correlation between the compound’s biological activities with their physicochemical substituents. The global parameters considered in this method include the electronic, steric, hydrophobic, and other effects that use multiple correlation methodology (IUPAC). Application of the Hansch analysis includes the Quantitative Structure-Activity Relationship (QSAR). This application develops correlations between activity of the ligands and their properties. As a rule of the thumb, the Hansch model “gives information about the number of parameters to be selected for regression analysis in QSAR based on the number of compounds”.1 Applications of QSAR is used in classification, prediction of activity, diagnosis of mechanism of drug action, environmental chemistry, toxicity prediction, and optimization of lead compound. Descriptors used include:2
Spatial descriptors – where the solvent-accessibility of the molecules surface areas and their charges are described
Electronic descriptors – the charge and electron orientations are described
Topological descriptors – description is based from the structural and graphical concepts as well as geometric features such as size, shape, and branching
______________________________
1 Narasihan, B. “QSAR by Hansch Analysis”. Journal of Pharmaceutical and BioSciences. (nd)
2 Theochem. “QSAR and QSPR” (nd).
Thermodynamic descriptors – the energy and conversions of the molecules are described
Quantum Mechanical descriptors – calculated descriptors that use semi-empirical methods that are considered to be accurate
The QSAR is a routine tool used in the medicinal chemistry to analyze large sets of molecules that are candidate to become drugs. Improved techniques through this application include the selection of tests and training sets, cross validation, observation of autocorrelation between parameters, and detection and removal of outliers.3
Free Wilson Analysis
Free Wilson model is a method used in medicinal chemistry that shows the quantitative descriptions of the relationships of the structure activities. It provides direct relationship of the biological properties and structural features. The method is based upon the mathematical model where a particular substituent at a specific position assumed to make constant and additive contribution to the molecules’ biological activity in a series of molecules with chemical relationships. The approach of free Wilson analysis is widely used in QSR. It is ore simple and fast, and the methods are cheap due to no required substitution of constants such as sigma, pi, and others. The efficiency of this method is high such that the greater is the structure’s complexity, the larger is the potentiality and possibility of the substituents at desired positions. It is also very effective in situations when the constants are not available.4
__________________________
3 Theochem. “QSAR and QSPR” (nd).
4 Kumar, P. “Drug Design”. SLT Institute of Pharmaceutical Sciences. (2014).
COMFA or Comparative Molecular Field Analysis is a technique of the 3D QSAR that is based on data of active molecules. Mostly, this technique is applied when the 3D structure of the receptor is not yet known. The significance of COMF is for the derivation of the correlation between the biological activities of a given set of molecules and their 3D characteristics such as the shape and bonds.5
COMSIA or Comparative Molecular Similarity Indices Analysis is one of the modern 3D QSAR mehods developed at BASF Ludwigshafen Germany. CoMSIA technique that is used in drug discovery considers the electrostatic and steric features, hydrogen bond acceptor and donor, and the hydrophobic fields. 6
HQSAR or the Hologram QSAR is a method that does not require the exact and accurae 3D information of ligands. This method used molecules that are hashed to molecular fingerprints encoding the frequency of the occurrence of the various types of molecular fragments. These fragment sizes control the maximum and minimum lengths of the fragments that are included in the hologram fingerprint. It works through the identification of the pattrns of the substructural frgens that are related to the bioactive molecules cytotoxic activities.7
__________________________
5 Ott, M. “Comparative Molecular Field Analysis (CoMFA)”. (nd).
6 Suh, ME., Park, SY., and Lee, HJ. “Comparison of QSAR methods 9CoMFA, CoMSIA, HQSAR) of Antiancer 1-N-Substituted Imidazoquinoline-4,9-dione Derivatives”. Bull Korean Chem. Soc. Vol 3, No. 3. (2002).
7 Ibid.
References:
IUPAC. Compendium of Chemical Terminology, 2nd ed (the “Gold Book). Compiled by A.D.
McNaught and A. Wilkinson. Blackwell scientific Publications, Oxford. (1997).
Kumar, P. “Drug Design”. SLT Institute of Pharmaceutical Sciences. (2014).
Narasihan, B. “QSAR by Hansch Analysis”. Journal of Pharmaceutical and BioSciences.
Ott, M. “Comparative Molecular Field Analysis (CoMFA)”. (nd). Accessible through
http://www.cmbi.ru.nl/edu/bioinf4/comfa-Prac/comfa.shtml
Suh, ME., Park, SY., and Lee, HJ. “Comparison of QSAR methods 9CoMFA, CoMSIA,
HQSAR) of Antiancer 1-N-Substituted Imidazoquinoline-4,9-dione Derivatives”. Bull Korean Chem. Soc. Vol 3, No. 3. (2002).
Theochem. “QSAR and QSPR” (nd). Accessible through
https://www.theochem.kth.se/courses/molmod/lectures/lecture14.pdf
