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Free wilson analysis

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ASHOK GAUTAM
ASHOK GAUTAM

The Free-Wilson approach correlates the biological activity of parent structures and analogues bearing different substituents. In 1964, Free and Wilson derived a mathematical model representing structural features as 1s and 0s correlated to biological activity. The method assumes substituents make additive contributions to biological activity. Free-Wilson analysis directly relates structural features to biological properties using only presence/absence of substituents as descriptors. It represents activity as the sum of group contributions and a reference compound activity. Drawbacks include needing substitution at two positions and only predicting combinations previously analyzed.

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Free Wilson Analysis By :- Ashok Gautam Skb college of pharmacy, kamptee
Free Wilson Analysis The Free-Wilson approach is truly a structure-activity based methodology in which the biological activity of the parent structure is measured and compared with the activity of analogues bearing different substituents Parent structure Activity of analogues bearing different substituent's Biological activity measured and compared with
In 1964, Free and Wilson derived a mathematical model that describes the presence and absence of certain structural features, i.e. those groups that are represented by the values 1 or 0 that correlate the resulting structural matrix with biological activity values The method of Free and Wilson is based upon an additive mathematical model in which a particular substituent in a specific position is assumed to make an additive and constant contribution to the biological activity of a molecule
Free and Wilson reasoned that the biological activity for a set of analogues could be described by the contributions that substituents or structural elements make to the activity of a parent structure
Free-Wilson analysis is a regression technique using the presence or absence of substituents or groups as the only molecule descriptors in correlations with biological activity It is the only numerical method which directly relates structural features with biological properties, in contrast to Hansch analysis, where physicochemical properties are correlated with biological activity values
It is represented by equation BA = 裡 a i x i + 亮 Where, BA is the biological activity, 亮 is the activity contribution of reference compound , a i is the biological activity group contributions of the substituents X1, X2,Xi in the different positions P of compound, x i denotes the presence (x i = 1) or absence (x i = 0) of particular structural fragment
Drawbacks of Free Wilson analysis At least two different positions of substitution must be chemically modified Predictions can only be made for new combinations of substituent's already included in the analysis Single point determinations obscure the statistical results mostly centered on the large number of parameters and subsequent loss of the statistical degree of freedom.
In 1971, in an attempt to deal with limitations of this approach, Fujita and Ban proposed a simplified approach that solely focused on the additivity of group contribution. LogA/A0 = 裡 G i X i Where, A and A0 represents the biological activity of the substituted and unsubstituted compounds respectively, G i is the activity of the sustituent, X i had the value of 1 or 0 that corresponded to the presence or absence of that substituent.
Mixed Hansch/Free-Wilson model The similarity in approaches of Hansch analysis and Free-Wilson analysis allows them to be used within the same framework Log 1/C = ai + cj 个j + constant ai is the contribution for each ith substituent, 个j is any physicochemical property of a substituent Xj. This equation combines the advantages of Hansch and Free Wilson analysis and widens the applicability of both methods. Physicochemical parameters describe parts of the molecules with broad structural variation, whereas indicator variables ai (Free Wilson type variables) encode the effects of structural variations that cannot be described otherwise A recent study of the Pglycoprotein inhibitory activity of 48 propafenone-type modulators of multidrug resistance, using a combined Hansch/Free-Wilson approach was deemed to have higher predictive ability than that of a stand-alone Free-Wilson analysis
Free wilson analysis

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Free wilson analysis

  • 1. Free Wilson Analysis By :- Ashok Gautam Skb college of pharmacy, kamptee
  • 2. Free Wilson Analysis The Free-Wilson approach is truly a structure-activity based methodology in which the biological activity of the parent structure is measured and compared with the activity of analogues bearing different substituents Parent structure Activity of analogues bearing different substituent's Biological activity measured and compared with
  • 3. In 1964, Free and Wilson derived a mathematical model that describes the presence and absence of certain structural features, i.e. those groups that are represented by the values 1 or 0 that correlate the resulting structural matrix with biological activity values The method of Free and Wilson is based upon an additive mathematical model in which a particular substituent in a specific position is assumed to make an additive and constant contribution to the biological activity of a molecule
  • 4. Free and Wilson reasoned that the biological activity for a set of analogues could be described by the contributions that substituents or structural elements make to the activity of a parent structure
  • 5. Free-Wilson analysis is a regression technique using the presence or absence of substituents or groups as the only molecule descriptors in correlations with biological activity It is the only numerical method which directly relates structural features with biological properties, in contrast to Hansch analysis, where physicochemical properties are correlated with biological activity values
  • 6. It is represented by equation BA = 裡 a i x i + 亮 Where, BA is the biological activity, 亮 is the activity contribution of reference compound , a i is the biological activity group contributions of the substituents X1, X2,Xi in the different positions P of compound, x i denotes the presence (x i = 1) or absence (x i = 0) of particular structural fragment
  • 7. Drawbacks of Free Wilson analysis At least two different positions of substitution must be chemically modified Predictions can only be made for new combinations of substituent's already included in the analysis Single point determinations obscure the statistical results mostly centered on the large number of parameters and subsequent loss of the statistical degree of freedom.
  • 8. In 1971, in an attempt to deal with limitations of this approach, Fujita and Ban proposed a simplified approach that solely focused on the additivity of group contribution. LogA/A0 = 裡 G i X i Where, A and A0 represents the biological activity of the substituted and unsubstituted compounds respectively, G i is the activity of the sustituent, X i had the value of 1 or 0 that corresponded to the presence or absence of that substituent.
  • 9. Mixed Hansch/Free-Wilson model The similarity in approaches of Hansch analysis and Free-Wilson analysis allows them to be used within the same framework Log 1/C = ai + cj 个j + constant ai is the contribution for each ith substituent, 个j is any physicochemical property of a substituent Xj. This equation combines the advantages of Hansch and Free Wilson analysis and widens the applicability of both methods. Physicochemical parameters describe parts of the molecules with broad structural variation, whereas indicator variables ai (Free Wilson type variables) encode the effects of structural variations that cannot be described otherwise A recent study of the Pglycoprotein inhibitory activity of 48 propafenone-type modulators of multidrug resistance, using a combined Hansch/Free-Wilson approach was deemed to have higher predictive ability than that of a stand-alone Free-Wilson analysis