Current Issue : April - June Volume : 2018 Issue Number : 2 Articles : 5 Articles
The newer antiviral molecule is the need at the current situation because of drug resistance in antiviral treatment. First generation Nonnucleoside reverse transcriptase inhibitors (NNRTI) are playing a crucial role in the treatment of HIV infection. Pharmacophore modeling of designed compound is a predictive tool to have higher success rate in drug discovery. In this article series of isatin derivative were designed and pharmacophore modeling was performed. Designed molecules were docked with the crystal structure of proteins and passed through ADME (absorption, distribution, metabolism and excretion) screening....
The present research deals with Maestro 9.1 assisted in-silico molecular docking exploration of anti-bacterial activity of the two macrolactin compounds; (R,E)-(3Z,5E,8S,9E,11Z,14R,16R,17E,19Z,24R)-14,16-dihydroxy-24-methyl-2-oxooxacyclotetracosa-3,5,9,11,17,19-hexaen-8-yl-5-hydroxyhept-3-enoate (1) and (R)-(3Z,5E,7S,9E,11Z,14R,16R,17E,19Z,24S)-14,16-dihydroxy-24-methyl-2-oxooxacyclotetracosa-3,5,9,11,17,19-hexaen-7-yl-6-(4-acetylphenyl)-5-hydroxyhexanoate (2) against the most common and primitive microorganism, Escherichia coli (E. coli) by inhibiting the molecular target fatty acid metabolism regulator protein (FadR) (PDB ID: 1H9G). Inhibition of this bacterial transcription factor stops the coordinated machinery that promotes fatty acid beta-oxidation and enzyme expression in fatty acid biosynthesis process. This ultimately leads to protein function inhibition, slows the growth, and eventually causes the fatal death of E. coli bacteria. The macrolactin compounds expressed potent interaction with the biological target FadR. From the study, compound 2 was observed to be the most active candidate that interacts better with the enzyme active site. The results presented a good correlation between the IFD binding scores and the inhibitory activity of compounds. The results concluded that these macro-structures will inhibit the FadR in a better way and may open several new avenues for designing better metabolic inhibitors in future for combating bacterial infections....
Fatty acid metabolism protein (FadR) is the most common and imperative biological target in E. coli, therefore inhibition of this molecular target by designed inhibitor will result in effective inhibition of microbial growth by crippling the metabolic functioning machinery. The present research aimed at exploring the FadR inhibitory potential of two furan-2-yl compounds; (E)-methyl-5-((3R,4R,6S,7R)-3-(2-(furan-2-yl)ethyl)-7-hydroxy-4-(3-methylbut-2-enyl)-octahydro-2H-chromen-6-yl)-4-methylpent-4-enoate (1) and methyl 3-((4aR,7S,8aR)-7-((3S,4R,E)-1-(furan-2-yl)-3-(hydroxymethyl)-7-methyloct-5-en-4-yl)-3,4,4a,5,6,7,8,8a-octahydronaphthalen-2-yl)propanoate (2) employing molecular docking studies against the target (PDB ID: 1H9G), by utilizing the Glide module of the Maestro 9.1 software. The best pose of compound 2 stated the most effective FadR inhibition with Glide score of -13.68 Kcal/mol whereas the score of compound 1 was found to be -13.23 Kcal/mol. Based on the crystal structure of the molecular target, the compound 2 formed a strong hydrogen bond with Asp145 via hydroxyl-group of the furan moiety in docking complex whereas the branched oxygen atom present in the hydroxyl group of compound 2 made hydrogen bonding with the amino acid residue Leu165. The water molecule present in the protein also formed hydrogen bonding with the Asp145. From this study, it can be concluded that the furan-2-yl containing compounds hold the potential to exhibit bacteriocidal activity by disrupting the fatty acid beta-oxidation and enzyme expression in fatty acid biosynthesis process when the key target fatty acid metabolism protein enzyme (FadR) was blocked successfully....
Vibrio vulnificus is the leading cause of seafood‐related fatality in the USA leading to more than 50% fatality. The fatty acid metabolism is regulated by the FadR protein in V. vulnificus. FadR mutants are unable to cause skin lesions and systemic liver infection in mice, symptoms that are typically observed when mice are infected with wild type V. vulnificus. Therefore, we hypothesize that inhibiting FadR could be used as a method to prevent and/or treat infection of mammalian hosts infected. The goal of present investigation involved discovery of some bacterial protein inhibitors, which ultimately cause the bactericidal effect. This was attempted by identifying certain metabolic processes or functions within the bacterial cell that, if inhibited, could slow growth, interrupt gene expression, or inhibit protein function. We screened the two furan containing compounds; methyl 3-((6R)-4-((R,E)-3-methylpent-1-en-1-yl)-4,4a,5,6,7,8,8a,9-octahydronaphtho[2,3-b]furan-6-yl)propanoate (1) and based (5aR,7S,8R,9aR)-7-isopentyl-8-methoxy-5a,6,7,8,9,9a-hexahydronaphtho[2,1-b]furan (2) as FadR inhibitor utilizing in silico molecular docking method using the Maestro 9.1 software. The present study indicated that both the furan based inhibitors 1 and 2 were found to be potent FadR antagonists. The Glide score of compound 1 and 2 were observed to be -12.57 and –10.20, respectively. Both the compounds demonstrated the formation of hydrogen bonds via oxo-group of the furan moiety with the amino acid residue Asp145. Compound 1 showed π-π stacking interactions with Phe180 and Tyr172 whereas amino acid residue Arg105 made π-cation interaction for both the inhibitors. The research provided a direction for the rational design of anti-microbial inhibitors by aiming the molecular protein targets....
The current investigation is a molecular docking study which involves exploration of anti-inflammatory potentials of two pyran molecules; 2-(but-3-en-1-yl)-5-nonyltetrahydro-2H-pyran (1) and 5-(7-butoxydodecyl)-2-(2-ethylbut-3-en-1-yl)-3,6-dihydro-2H-pyran (2) as non steroidal anti-inflammatory candidates (NSAIC) by inhibiting the most imperative biological target COX-2, utilizing Glide module of Maestro 9.1 software. Additionally, abbreviated ADME studies were performed using QikProp module to determine the significant parameters such as probable toxic effects, pharmacokinetic profiling and suitability in oral administration of the candidates. The amino acid residue Gln 172 seems to play a major role in the protein-ligand interaction. Both the structures 1 and 2 successfully made hydrogen bonding interaction with the inflammatory target COX-2. Structure 2 fits relatively more stable at the active site of COX-2 owing to the formation of one more stable hydrogen bonds with Thr 181 and also having a higher Glide score (-8.28 kcal/mol) than the structure 1 (-8.01 kcal/mol). The two compounds have the perspective of desired pharmacokinetic and safety profile....
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