Molecular Dynamics Simulation Study and Hybrid Pharmacophore Model Development in Human LTA4H Inhibitor Design

Human leukotriene A4 hydrolase (hLTA4H) is a bi-functional enzyme catalyzes the hydrolase and aminopeptidase functions upon the fatty acid and peptide substrates, respectively, utilizing the same but overlapping binding site. Particularly the hydrolase function of this enzyme catalyzes the rate-limiting step of the leukotriene (LT) cascade that converts the LTA4 to LTB4. This product is a potent pro-inflammatory activator of inflammatory responses and thus blocking this conversion provides a valuable means to design anti-inflammatory agents. Four structurally very similar chemical compounds with highly different inhibitory profile towards the hydrolase function of hLTA4H were selected from the literature. Molecular dynamics (MD) simulations of the complexes of hLTA4H with these inhibitors were performed and the results have provided valuable information explaining the reasons for the differences in their biological activities. Binding mode analysis revealed that the additional thiophene moiety of most active inhibitor helps the pyrrolidine moiety to interact the most important R563 and K565 residues. The hLTA4H complexes with the most active compound and substrate were utilized in the development of hybrid pharmacophore models. These developed pharmacophore models were used in screening chemical databases in order to identify lead candidates to design potent hLTA4H inhibitors. Final evaluation based on molecular docking and electronic parameters has identified three compounds of diverse chemical scaffolds as potential leads to be used in novel and potent hLTA4H inhibitor design

Micropropagation prospective of cotyledonary explants of <i>Decalepis hamiltonii</i> Wight & Arn.—An endangered edible species

256-260The study was undertaken to standardize the development of callus, shoot and root regeneration from cotyledonary explant of Decalepis hamiltonii Wight & Arn. through the tissue culture techniques. The MS medium supplemented with 6-benzyl amino purine (BA), 2,4-dichlorophenoxy acetic acid (2,4-D), kinetin (Kn), gibberelic acid (GA3), indole acetic acid (IAA), indole butyric acid (IBA) and 1-naphthalene acetic acid (NAA) was used for callus, shoot and root regeneration. The maximum percentage (82.0%)of callus formation was achieved on 0.5 mg/L BA in combination with 0.05 mg/L Kn, followed by 78.5% of callus formation on 0.5 mg/L 2,4-D fortified with 0.05 mg/L Kn. The highest shoot proliferation (4.6 shoots/callus) and shoot length (6.9 cm) was achieved on 1.0 mg/L BA combined with 0.1 mg/L GA3, followed by 3.8 shoots per callus and 5.8 cm shoot length on 1.0 mg/L IAA combined with 0.1 mg/L GA3. The highest root formation (38.2 roots/shoot) and root length (11.8cm) was achieved on ½ strength MS medium fortified with 0.4 mg/L IBA, followed by 36.5 roots per shoot and root length of 10.7 cm on 0.4 mg/L NAA. The well-developed rooted plantlets were hardened in the mixtures of forest soil, soil and vermiculite (1:1:1) and 97.5% plantlets survived after hardening