Smriti Khanna

Publications (12)14.01 Total impact

• Article: Metformin and glitazones: does similarity in biomolecular mechanism originate from tautomerism in these drugs?

  Sandeep Sundriyal, Smriti Khanna, Rikta Saha, Prasad V. Bharatam
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  ABSTRACT: This theoretical study attempts to find out similarity between metformin and glitazone class of antidiabetic drugs. It was found that some tautomeric forms of both metformin and thiazolidinedione ring of glitazones have similar molecular electrostatic potential (MESP) surface and may bind to a common complementary surface. Complexation and docking studies were also carried out in order to support this hypothesis.
  J. Phys. Org. Chem. 01/2008; 21:30–33.
• Source

  Available from: johnwiley.com.au

  Chapter: Modeling and Informatics in Drug Design

  Prasad V. Bharatam, Smriti Khanna, Sandrea M. Francis
  08/2007: pages 1 - 45; , ISBN: 9780470249031
• Article: Synthesis, in vitro and in silico evaluation of l-tyrosine containing PPARalpha/gamma dual agonists.

  Rakesh Kumar, Uma Ramachandran, Smriti Khanna, Prasad V Bharatam, Suryaprakash Raichur, Ranjan Chakrabarti
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  ABSTRACT: A novel series of l-tyrosine derivatives have been reported with potential PPARalpha/gamma dual agonistic activity. In vitro cell based PPARalpha/gamma transactivation studies have shown compound 4a and compound 4f to be the most potent PPARgamma and PPARalpha activators, respectively. Molecular docking studies performed on these series of compounds have complemented the experimental results and have led to interesting inferences.
  Bioorganic & Medicinal Chemistry 03/2007; 15(3):1547-55. · 2.92 Impact Factor
• Article: Evaluation of glycolamide esters of indomethacin as potential cyclooxygenase-2 (COX-2) inhibitors.

  Smriti Khanna, Manjula Madan, Akhila Vangoori, Rahul Banerjee, Ram Thaimattam, S K Jafar Sadik Basha, Mullangi Ramesh, Seshagiri Rao Casturi, Manojit Pal
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  ABSTRACT: A number of novel indomethacin glycolamide esters were synthesized and tested for their cyclooxygenase (COX-1 and COX-2) inhibition properties in vitro. Many of these compounds proved to be selective COX-2 inhibitors, and subtle structural changes in the substituents on the glycolamide ester moiety altered the inhibitory properties as well as potencies significantly. Their in vitro data were rationalized through molecular modeling studies. Few of them displayed anti-inflammatory activity in vivo. Compound 32, [1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid 2-morpholin-4-yl-2-oxo ethyl ester, was identified as a promising compound in this class and its good anti-inflammatory activity was demonstrated in the in vivo model.
  Bioorganic & Medicinal Chemistry 08/2006; 14(14):4820-33. · 2.92 Impact Factor
• Chapter: In silico Studies on PPARγ Agonistic Heterocyclic Systems

  Smriti Khanna, Raman Bahal, Prasad V. Bharatam
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  ABSTRACT: Several heterocyclic derivatives like oxazolidinediones, thiazolidinediones, tetarazoles, phenoxazines, etc. are being developed for the treatment of insulin resistance and type 2 diabetes mellitus. The heterocyclic head group in these systems binds to and activates Peroxisome Proliferator Activated Receptor γ, (PPARγ) anuclear receptor that regulated the expression of several genes involved in the metabolism. Non-heterocyclic natural ligands like eicosonoids, prostaglandin are only weekly active against this target. Some of PPARγ agonistic agents like rosiglitazone, pioglitazone, are in daily use as anti-diabetic agents worldwide. Molecular modeling studies are being employed to study the chemistry, biology and pharmacological issues of these compounds. In this review studies based three-dimensional quantitative structure activity relationship (3D-QSAR) on the design of new chemical entities, molecular docking studies in understanding the drug receptor interactions, pharmacophore mapping studies in analyzing the important pharmacophore features and performing virtual screening, pharmacoinformatics studies in identifying new scaffolds, quantitative chemical studies in understanding the electronic structure and reactivity of these heterocyclic systems are reviewed.
  01/2006: pages 149-180;
• Article: Additivity of molecular fields: CoMFA study on dual activators of PPARalpha and PPARgamma.

  Smriti Khanna, M E Sobhia, Prasad V Bharatam
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  ABSTRACT: Recent trends in drug discovery include methods to identify dual and triple activating drugs. This approach is being successfully employed in malaria, cancer, asthma, insulin resistance, etc. Molecular field analysis has been employed in correlating pharmacological data and field parameters. In this paper we introduce the concept of additivity of molecular fields to correlate molecular fields of dual activators and their pIC(50) values. PPARalpha and PPARgamma dual activators, which affect hypertriglyceridemia and hyperglycemia, have been chosen to validate the molecular field additivity concept. Three CoMFA models namely alpha-model, gamma-model and dual-model have been developed. The validity of this concept has been ascertained by (a) comparing contour maps, (b) by comparing CoMFA results with FlexX docking results and (c) by analyzing newly designed molecules.
  Journal of Medicinal Chemistry 05/2005; 48(8):3015-25. · 5.25 Impact Factor
• Article: Additivity of Molecular Fields:  CoMFA Study on Dual Activators of PPARα and PPARγ

  Smriti Khanna, M. E. Sobhia, Prasad V. Bharatam
  [show abstract] [hide abstract]
  ABSTRACT: Recent trends in drug discovery include methods to identify dual and triple activating drugs. This approach is being successfully employed in malaria, cancer, asthma, insulin resistance, etc. Molecular field analysis has been employed in correlating pharmacological data and field parameters. In this paper we introduce the concept of additivity of molecular fields to correlate molecular fields of dual activators and their pIC50 values. PPARα and PPARγ dual activators, which affect hypertriglyceridemia and hyperglycemia, have been chosen to validate the molecular field additivity concept. Three CoMFA models namely α-model, γ-model and dual-model have been developed. The validity of this concept has been ascertained by (a) comparing contour maps, (b) by comparing CoMFA results with FlexX docking results and (c) by analyzing newly designed molecules.
  03/2005;
• Article: Rapid Racemization in Thiazolidinediones:  A Quantum Chemical Study†

  Prasad V. Bharatam, Smriti Khanna
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  ABSTRACT: Ab initio molecular orbital (MO) and density functional studies have been carried out on the keto−enol tautomerization process in thiazolidinediones to understand the mechanism of rapid racemization observed in these systems. MP2(full)/6-31+G* results on model thiazolidinedione 1 indicate that the energy difference between keto and enol tautomers is 24.04 kcal/mol, which is larger than that in acetaldehyde (16.23 kcal/mol). Neither the ring strain in 1 nor the electron delocalization in its tautomers is significant enough to facilitate rapid racemization through this mechanism. Reversible S-oxide formation increases the acidity of the hydrogen at the chiral center as well as provides an alternative path for tautomerization, suggesting that such a mechanism is responsible for the rapid racemization observed under physiological conditions.
  04/2004;
• Article: Studies on some glitazones having pyridine as the linker unit.

  Uma Ramachandran, Alka Mital, Prasad V Bharatam, Smriti Khanna, Poduri Rama Rao, Krishnamoorthy Srinivasan, Rakesh Kumar, Harmander Pal Singh Chawla, Chaman Lal Kaul, Suryaprakash Raichur, Ranjan Chakrabarti
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  ABSTRACT: Molecular modeling on various well-known glitazones carrying a pyridine ring instead of benzene ring as the middle linker unit showed conformational rigidity as compared to their parent molecules. Blocking the lone pair of electrons on the pyridine N, made them flexible once again. A few representatives of these analogues were synthesized and their efficacy as PPARgamma agonists evaluated.
  Bioorganic & Medicinal Chemistry 03/2004; 12(4):655-62. · 2.92 Impact Factor
• Article: Synthesis, in vitro and in silico evaluation of l-tyrosine containing PPARα/γ dual agonists

  Rakesh Kumar, Uma Ramachandran, Smriti Khanna, Prasad V. Bharatam, Suryaprakash Raichur, Ranjan Chakrabarti
  Bioorganic & Medicinal Chemistry. 15(3):1547-1555.
• Article: Regioselective aluminium chloride induced heteroarylation of pyrrolo[1,2-b]pyridazines: its scope and application

  Manojit Pal, Venkateswara Rao Batchu, Smriti Khanna, Koteswar Rao Yeleswarapu
  Tetrahedron. 58(50):9933-9940.
• Article: Candida rugosa lipase mediated multigram synthesis of acid part of S(+)-atliprofen, a new NSAID and molecular modeling studies aimed at predicting selectivity of the enzyme

  Shilpi Mittal, Smriti Khanna, Animesh Roy, Prasad V. Bharatam, H.P.S. Chawla
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  ABSTRACT: An efficient procedure to prepare S-4-(3-thienyl)phenyl-α-methylacetic acid, an intermediate of a recently approved non-steroidal anti-inflammatory cyclooxygenase inhibitor atliprofen by enantioselective hydrolysis of the corresponding esters in presence of candida rugosa lipase is reported. The methyl and butyl esters of the racemic acid 2 were synthesized and subjected to enantioselective hydrolysis by the lipase to give S-4-(3-thienyl)phenyl-α-methylacetic acid upto 97.86% ee. The observed enantioselectivity during the hydrolysis of the substrate by the lipase was rationalized by molecular modeling studies. The methyl esters of both R and S-enantiomers of 4-(3-thienyl)phenyl-α-methylacetic acid, naproxen and ketoprofen were taken for the modeling studies. The results of the modeling studies are in conformity with the experimental observations.
  Enzyme and Microbial Technology.