DFT Based Atomic Softness and Its Application in Site Selectivity

Singh, Priti; Pasha, Farhan Ahmad; Srivastava, Harshita

doi:10.1002/qsar.200330828

Cited by 26 publications

(21 citation statements)

References 38 publications

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“…It is well established that the stability of the compound formed between nucleophile and electrophile depends upon the value of difference between softness values of E ‡ m of nucleophile and softness values of E ‡ n of electrophile, ∆E ‡ nm represent the difference. The higher is the ∆E ‡ nm (∆E ‡ nm = | E ‡ n-E ‡ m |) greater is the stability of the compound [22][23][24] . ∆E ‡ nm values, when the compounds treated as nucleophile and receptor amino acids (Asn-Y182, Tyr-Y183 and Glu-Y186) as electrophile, have shown that interaction occur between the compound (O/S-atom at site-2) and Asn Y182 amino acid (C-atom of carbonyl group of-CONH-), as the interaction have higher value of  ∆E ‡ nm than interaction between Tyr-Y183 and Glu-Y185, 186, Table 9.…”

Section: Discussionmentioning

confidence: 99%

Hydrophobic, Polar and Hydrogen Bonding Based Drug-Receptor Interaction of Tetrahydroimidazobenzodiazepinones

Sahu¹,

Khan²,

Singh³

et al. 2008

American J. of Immunology

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Anti-HIV drug discovery has been increasingly focusing on HIV-1-RT (reverse transcriptase) as a potential therapeutic target. Tetrahydroimidazobenzodiazepinone (TIBO) belongs to non-nucleoside group of reverse transcriptase inhibitors (NNRTIs). A computational chemistry study has been performed on a series of tetrahydroimidazo-benzodiazepinones as HIV-1-NNRT inhibitors. Problem statement: In order to search out new drug of desired activity from the lead compounds, there was need to know the interaction of drugs with their receptor i.e., type of force(s) that have predominant role. Approach: Log P and SASA have been used for measurement of hydrophobic interaction, energy of protonation for measurement of most favorable hydrogen bond acceptor site, bond length and bond strain for measurement of strength of hydrogen bond formed between drug and receptor, atomic charges, ionization potential, electronegativity, E ‡ n and E ‡ m and their difference ∆E ‡ nm for measurement of polar interaction. The 3D modeling and geometry optimization of the compounds and receptor amino acids have been done by semiempirical method with MOPAC2002 associated with CAChe software. Results: The study has shown that hydrophobic interaction is predominant and made major contribution, while hydrogen bonding and polar interactions help in proper orientation of the compound (or its functional groups) to make maximam interaction. Conclusion: In this study theoretical technique has been discussed by which new hypothetical HIV-1-NNRT inhibitors can be developed prior to their synthesis only by introducing effective hydrophobic substituents at specific sites.

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Section: Discussionmentioning

confidence: 99%

Hydrophobic, Polar and Hydrogen Bonding Based Drug-Receptor Interaction of Tetrahydroimidazobenzodiazepinones

Sahu¹,

Khan²,

Singh³

et al. 2008

American J. of Immunology

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“…These softness values are widely used to describe the QSAR study of different series of compounds (Singh et al, 2003(Singh et al, , 2004aPasha et al, 2005a, b). These softness values for a series of testosterone derivatives are available in a recently published work (Srivastava et al, 2005).…”

Section: Theory Of Dft-based Qsarmentioning

confidence: 99%

“…All descriptor values-except Klopman atomic softness E n à , which was reported by Srivastava et al (2005)-have been calculated using our own developed computer program (QDC) based on the equations given above. E n à values for the derivatives presented in Table 3 were calculated by using the modified Klopman equation (Singh et al, 1980(Singh et al, , 2003. Descriptor values were correlated with observed activities using multiple linear regression analysis to make a reliable and versatile QSAR model.…”

Section: Computational Detailsmentioning

confidence: 99%

“…Twenty-four hours after last injection the animals were autopsied and levator ani muscle, ventral prostate, and seminal vesicle were removed and their wet weight recorded. The therapeutic index is the ratio of levator ani muscle and ventral prostate (Sala and Baldratti, 1957) E n à Klopman atomic softness of the most acidic site of the parent skeleton for different derivatives calculated with the help of modified Klopman equation (Singh et al, 1980(Singh et al, , 2003, S global softness, M W molecular weight, PA activity predicted by using regression Eq. 10 a Data points not included in deriving regression equation Table 4.…”

Section: Fourth Setmentioning

confidence: 99%

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Novel applications of atomic softness and QSAR study of testosterone derivatives

Srivastava¹,

Pasha²,

Mishra³

et al. 2008

Med Chem Res

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Testosterone is an important steroidal hormone. The parent scaffold consists of 19 carbon atoms and acts via androgen receptor-directly or as 5a-dihydrotestosterone (DHT)-or by conversion into estradiol and activation of certain estrogen receptors. In silico assessment of activity towards their receptor was performed using quantum-chemical descriptors. Various essential indices were calculated using semiempirical parameterized model 3 (PM3) calculations. The descriptors values were statistically correlated using multiple linear regression analysis. Quantitative structure-activity relationship (QSAR) study indicated that the acidic properties of these derivatives have significant relationships with observed biological activity. Global acidic nature as well as atomic acidic character showed key interaction with the receptor. This study might be helpful to describe further ligands with improved activity.

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“…The method for calculation of electron affinity of an atom in a molecule (EA) has been described by us earlier [28] . Since The Local acidic softness En is a measure of electron accepting tendency while the electrophilicity index (ω) of a molecule has been introduced by Parr et al On the basis of these two important values we may derived a new parameter the partial electrophilicity ( ω p ) by multiplying local acidic softness En and elecrtophilicity index (w) as…”

Section: Theorymentioning

confidence: 99%

DFT Based Electrophilicity Index and QSAR study of Phenols as Anti Leukaemia Agent

Pasha¹,

Srivastava²,

Beg³

et al. 2006

American J. of Immunology

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Density Functional reactivity indices based QSAR study of 49 phenol derivatives is presented in this paper. Two different models to describe the anti leukaemia activity of phenols have been made. First QSAR model includes molecular properties like molecular weight (Mw), hardness (η), chemical potential (µ), total energy, and electrophilicity index (ω). Various regression models have been made and regression quality indicates that these descriptors provides valuable information and have significant role in assessment of activity of phenols. Klopman gave first quantum chemical treatment to describe the reactivity of a chemical system in terms of acidic softness E n and basic softness E m at atomic level. In this paper we have derived the partial electrophilicity by the multiplication of global electrophilicity index (given by Parr etal) and the acidic softness En (given by Klopman). This total electrophilicity index has been used as descriptors along with the other atomic properties like highest negative charge (Q min ) etc in second QSAR model. This model also provides good results. The DFT calculations have been performed by using B88-PW91 GGA energy functional with the DZVP basis set on Cache pro software and the regression models have been made on project leader software associated with CAChe. These DFT models have high predictive power and have sufficient reliability to describe the Anti leukaemia activity of phenols which is clear from its correlation coefficient r 2 and cross validation coefficient r cv 2 .

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DFT Based Atomic Softness and Its Application in Site Selectivity

Cited by 26 publications

References 38 publications

Hydrophobic, Polar and Hydrogen Bonding Based Drug-Receptor Interaction of Tetrahydroimidazobenzodiazepinones

Hydrophobic, Polar and Hydrogen Bonding Based Drug-Receptor Interaction of Tetrahydroimidazobenzodiazepinones

Novel applications of atomic softness and QSAR study of testosterone derivatives

DFT Based Electrophilicity Index and QSAR study of Phenols as Anti Leukaemia Agent

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