Ayaz Ahmed

Understanding LuxS-based quorum sensing and its inhibition – molecular dynamics simulation study

Abstract Molecular dynamics simulations were successfully applied to LuxS protein and its protein–ligand complex using the newly developed force field parameters for the iron containing active site. To the best of our knowledge, this was the first attempt to develop force field parameters for the iron containing active site of the LuxS protein. From the simulations, catalytically important amino acid residues were identified which were found to stabilise the ligand. Two residues Glu57 and Asp77 were involved in polar interactions while the protein region in the range between amino acid residue 125 and 131 were predicted to facilitate the entry of ligand to the active site. Other residues like Arg65, Asp77, Ile78 and Ser79 were also recognised as ligand stabilising factors deduced from the simulation. These results were also found to be in good agreement with earlier studies and thus demonstrated the successful application of MD simulations to the LuxS protein. Moreover, the simulation data were expected to be considered for the development of rational approaches in order to identify new LuxS-based quorum sensing antagonists for the treatment of pathologies caused by resistant bacteria.

Three new anthraquinone derivatives isolated from Symplocos racemosa and their antibiofilm activity

Three new alkyl substituted anthraquinone derivatives, trivially named as symploquinones A-C (Compounds 1-3) were isolated from Symplocos racemosa. The structures of these compounds were determined on the basis of extensive spectroscopic analyses (UV, IR, Mass, 1H- and 13C-NMR, and two-dimensional (2D) NMR techniques). The resulting data were also compared with the reported literature. These compounds were then subjected to antibacterial or antibiofilm testing. Compounds 1 and 3 exhibited good antibacterial activity in the concentration range of 160-83 μg·mL-1 against Streptococcus mutans, methicillin resistant Staphylococcus aureus and Proteus mirabilis. Both compounds were further screened for anti-biofilm activity, which revealed promising activities at sub-MIC concentrations. None of the compounds were found to be active against Klebsiella pneumoniae.

Isolation and Characterization of Two New Secondary Metabolites From Quercus incana and Their Antidepressant- and Anxiolytic-Like Potential

The ethyl acetate fraction of Quercus incana yielded two new compounds [1 and 2]. The characterization and structure elucidation of these compounds were carried out through various spectroscopic techniques such as mass spectrometry along with one- and two-dimensional NMR techniques. The structural formula was deduced to be 2-(4-hydroxybutan-2-yl)-5-methoxyphenol [1] and 4-hydroxy-3-(hydroxymethyl) pentanoic acid [2]. The elevated plus maze (EPM) and light–dark box (LDB) tests (classical mouse models) were performed in order to reveal the anxiolytic potential of both compounds [1 and 2]. Both compounds displayed dose-dependent increases in open-arm entries and time spent in open arms in EPM (∗P < 0.05, ∗∗P < 0.01), and increased the time spent in the lit compartment and increased transitions between the two compartments in LDB test (∗P < 0.05, ∗∗P < 0.01). Co-administration of selective benzodiazepine (BZP) receptor antagonist, flumazenil (2.5 mg/kg) with compounds [1 and 2] decreased the anxiolytic-like activity of both compounds in the EPM indicating BZP-binding site of GABA-A receptors are involved in the anxiolytic-like effect. Similarly, both compounds at the dose level of 10 and 30 mg/kg, i.p. exerted pronounced antidepressant-like effect in both forced swimming as well as tail suspension tests (∗P < 0.05, ∗∗P < 0.01; ANOVA followed by Dunnett’s post hoc test). The effect at 30 mg/kg was comparable to the reference drug imipramine (60 mg/kg).