NOPR Collection:

A quantitative structure-activity relationship (QSAR) study on a few series of potent, highly selective inhibitors of nitric oxide synthase

2014-02-01T00:00:00Z

Title: A quantitative structure-activity relationship (QSAR) study on a few series of potent, highly selective inhibitors of nitric oxide synthase Authors: Bharti, Vishwa Deepak; Gupta, Satya P; Kumar, Harish Abstract: QSAR study was performed on a series of 1,2-dihydro-4-quinazolinamines, 4,5-dialkylsubstituted-2-imino-1,3-thiazolidine derivatives and 4,5-disubstituted-1,3-oxazolidin-2-imine derivatives studied by Tinker et al. [J Med Chem (2003), 46, 913-916], Ueda et al. [Bioorg Med Chem (2004) 12, 4101-4116] and Ueda et al. [Bioorg Med Chem Lett (2004) 14, 313-316], respectively, as potent, highly selective inhibitors of inducible nitric oxide synthase (iNOS). The iNOS inhibition activity of the whole series of compounds was analyzed in relation to the physicochemical and molecular properties of the compounds. The QSAR analysis revealed that the inhibition potency of the compounds was controlled by a topological parameter ¹^v (Kier’s first order valence molecular connectivity index), density (D), surface tension (St) and length (steric parameter) of a substituent. This suggested that the drug-receptor interaction predominantly involved the dispersion interaction, but the bulky molecule would face steric problem because of which the molecule may not completely fit in active sites of the receptor and thus may not have the optimum interaction. Page(s): 29-36

Study of photodynamic, sonodynamic and antioxidative influence on HeLa cell line

2014-02-01T00:00:00Z

Title: Study of photodynamic, sonodynamic and antioxidative influence on HeLa cell line Authors: Tomankova, Katerina; Kolarova, Hana; Vachutka, Jaromir; Zapletalova, Jana; Hanakova, Adela; Kaplova, Eva Abstract: Photodynamic treatment (PDT) in combination with sonodynamic treatment (SDT) can be used as suitable methods to treat malignant and benign diseases or combat resistant bacteria. Both methods affect the production of reactive oxygen species (ROS). On the other hand, antioxidants are useful for cell protection against ROS. This work was aimed to study the effect of PDT and SDT treatments on the HeLa cell line using antioxidant Pronalen Sensitive Skin® as a protection from free radicals in the cells. We evaluated the effect of sensitizer ClAlPcS₂ using battery of in vitro methods, including MTT assay, kinetic production of ROS, mitochondrial membrane potential change, type of cell death and microscopic analysis. Ultrasound treatment was observed to increase the production of ROS, only in combination with PDT, particularly at higher concentrations of ClAlPcS₂. The added antioxidant acts as protection against free radicals and has potential as a dietary supplement against aging or free radicals. The results of study suggested that ClAlPcS₂ could be used as a potential photosensitizer for treatment of a specific type of cancers. Page(s): 19-28

Conformational study of N-methylated alanine peptides and design of A inhibitor

2014-02-01T00:00:00Z

Title: Conformational study of N-methylated alanine peptides and design of A inhibitor Authors: Nandel, Fateh S; Jaswal, Radhika R Abstract: N-Methylation increases the proteolytic stability of peptides and leads to improved pharmacological and increased nematicidal property against plant pathogens. In this study, the quantum mechanical and molecular dynamic simulation approaches were used to investigate conformational behavior of peptides containing only N-methylated alanine (NMeAla) residues and N-methylated alanine and alanine residues at alternate positions. The amide bond geometry was found to be trans and the poly NMeAla peptides were shown to populate in the helical structure without hydrogen bond with , values of ~ 0, 90˚ stabilized by carbonyl-carbonyl interactions. Molecular dynamic simulations in water/methanol revealed the formation of β-strand structure, irrespective of the starting geometry due to the interaction of solvent molecules with the carbonyl groups of peptide backbone. Analysis of simulation results as a function of time suggested that the opening of helical structure without hydrogen bond started from C-terminal. Conformational behavior of peptides containing N-MeAla and Ala was used to design Ab peptide inhibitor and the model tetrapeptide Ac-Ala-NMeAla-Ala-NHMe in the β-strand structure was shown to interact with the hydrophobic stretch of Aβ15-42 peptide. Page(s): 7-18

New mathematical derivations for calculation of ATP yield due to the complete oxidation of different types of fatty acids

2014-02-01T00:00:00Z

Title: New mathematical derivations for calculation of ATP yield due to the complete oxidation of different types of fatty acids Authors: Reddy, Banda Venkat; Prasad, Bommena Rajendra; Sinha, Sukesh Narayan; Ahmed, Noor Abstract: During the complete oxidation of fatty acids, the electrons removed from fatty acids in different forms (FADH₂ and NADH₂) pass through the respiratory chain, driving the ATP synthesis. Generally, the ATP yield due to the complete oxidation of fatty acids is calculated by sum total the ATPs obtained due to the oxidation of FADH₂ and NADH₂due to lack of any particular method. This calculation is simple for saturated even numbered fatty acids, but in the case of saturated and unsaturated odd numbered fatty acids the calculation of ATP yield is difficult and needs mathematical calculations due to some changes in their β-oxidation pathway when compared to the pathway of saturated even numbered fatty acids. These calculations are made simple by our derivations and following formulae where we require only number of carbon atoms and double bonds present in a fatty acid. Our method is superior and easier in comparison to long mathematical calculations that are in the practice.

Page(s): 52-57