Usama Shaheen

Computational evaluation and experimental verification of antibacterial and antioxidant activity of 7-hydroxy-3-pyrazolyl-4H-chromen-4-ones and their o-glucosides: identification of pharmacophore sites

This paper reports the computational evaluation and experimental verification of 7-hydroxy-3-(1-phenyl-3-aryl-1H-pyrazol-5-yl)-4H-chromen-4-ones 3 and their o-β-d-glucopyranosides 5 for their antimicrobial and antioxidant activity. The prepared compounds were tested against various Gram-positive and Gram-negative bacteria species. Some of the synthesized compounds have shown potential antimicrobial and antioxidant activity. This POM bioinformatic study could greatly help to pharmacomodulate the potential antibiotics and antioxidants.Graphical AbstractThis paper describes the computational POM (Petra/Osiris/Molinspiration) evaluation and experimental verification of 7-o-β-d-glucopyranosyloxy-3-(1-phenyl-3-aryl-1H-pyrazol-5-yl)-4H-chromen-4-ones and metabolites for their antimicrobial and antioxidant activity.

POM analyses of Raltegravir derivatives: a new reflection enlightening the mechanism of HIV-integrase inhibition

Petra/Osiris/Molinspiration analysis (POM) is a promising new bioinformatical approach to establish structure and activity correlations. In the present study, we have reported the POM analyses of Raltegravir analogues that have aimed to figure out the structural features of HIV-integrase inhibitory activity. The resulting model exhibited two controllable bidentate O, O-pockets taken into consideration contributions from the steric and electrostatic fields. The POM analysis has provided interesting insights into the understanding the steric and electronic structural requirements for HIV-IN inhibitory activity. Furthermore, all the molecules were subjected to the toxicity assessment using Molinspiration and Osiris calculations. Among the various HIV-IN inhibitors, compound 27 (Raltegravir) displayed optimum drug-like characteristic activity with low toxicity. The mechanism of HIV-integrase inhibition by different Raltegravir derivatives is also discussed. This study also concluded that the bioactivity of DKA analogues should be discussed on the basis of catalytic activity of bimetallic complexes, not just on the basis of DKA or Raltegravir/HIV-integrase interaction.

POM analyses of antimicrobial activity of some 2,3-armed 4,5,6,7-tetrahydro-1-benzothiophenes: favourable and unfavourable physico-chemical parameters in design of antibacterial and mycolytic agents

In the present contribution, we have used petra, osiris and molinspiration (POM) analyses to identify pharmacophores and anti-pharmacophores for antibacterial/antifungal activity of some benzothiophene derivatives (THBT). Lipophilicity and presence of tautomerism processes were the major factors that governed the orientation to antibacterial and/or antiviral activity. It was also observed that these compounds POM analyzed have a closed pharmacophore site which might be bioactivity low. Further, we have carried out receptor-based electrostatic analysis to confirm the electronic, steric and hydrophobic requirements for future modifications. The POM analyses provide substantial idea about the structural features responsible for their combined antibacterial/antifungal activity and provide guidelines for further modifications, with the aim of improving the activity and selectivity of designed drugs targeting potentially the drug-resistant microorganisms.Graphical AbstractThe impact of intramolecular OH/N and NH/N interactions on bioactivity of pharmacophores sites of THBT series 5–15 is established. The POM analyses of 2,3-armed 4,5,6,7-tetrahydro-1-benzothiophenes (THBT) 5–15 provide substantial idea about the structural features responsible for their failure as dual antibacterial/antifungal agents and provide guidelines for further modifications, with the aim of improving the activity and selectivity of designed drugs targeting potentially the bacterial and fungal enzymes responsible of diseases.

Synthesis, characterization, crystal structure determination and biological screening of novel N-1 and C5 alkyl substituted scaffolds of pyrimidine.

The novel N-1 and C5 alkyl substituted derivatives of pyrimidine were synthesized by using tetrabutyl ammonium bromide (TBAB) as phase transfer catalyst at 20-25 °C with excellent productivity (85-95%). The new compounds were evaluated for their antibacterial activities by screening them against Gram-positive and Gram-negative bacterial strain: Staphylococcus aureus ATCC 6538P, Salmonella abony NCTC 6017: Escherichia coli ATCC 8739, Staphylococcus epidermidis ATCC 12228. Among all compounds evaluated the molecule 2c and (2g-j) exhibit the most pronounced antibacterial activity against E. coli, S. aureus and S. abony with MICs value 25 μg/mL.

POM analyses for antimicrobial evaluation of thienopyrimidinones derivatives: a rapid method for drug design

AbstractIn this work, a new and efficient strategy to identify pharmacophores and anti-pharmacophores sites in thienopyrimidinone derivatives for antibacterial/antifungal activity using Petra, Osiris and Molinspiration (POM) analyses is described. We carried out receptor based electrostatic analysis to confirm the electronic, steric and hydrophobic requirements for further modifications. Results showed that the major factors that govern the orientation to antibacterial/antiviral activity were of lipophilicity and presence of tautomerism. In addition, POM analyzed compounds constitute different supplementary attractive active sites that possess significant bioactivity and qualify them as promising candidates that might be responsible to inhibit kinase enzymes. Furthermore, the POM analyses provide substantial idea about the structural features of thienopyrimidinone derivatives in relation to biological activities against disease causing agents. Our results suggest future work on these POM assessed derivatives to evaluate their toxicity in human cells and selectivity which improve activity against cancer causing kinase enzymes by developing target oriented new drugs to save humanity.Graphical AbstractThe identification of potential combined antibacterial/ antifungal and antitumor pharmacophores sites of 4-12, using POM analyses, is the crucial step in optimization of hits. The POM analyses of thienopyrimidinones 4-12 provide substantial idea about the structural features responsible for their combined antibacterial/antifungal activity and provide guidelines for further modifications, with the aim of improving the activity and selectivity of designed drugs targeting potentially the kinase enzyme responsible of cancer.

Antihypertensive and vasodilator effects of methanolic extract of Inula viscosa: Biological evaluation and POM analysis of cynarin, chlorogenic acid as potential hypertensive

BACKGROUND Inula viscosa L. (Asteraceae) is a medicinal plant widely used as a folk medicine in oriental Morocco, to treat hypertension. The antihypertensive effect of the methanolic extract obtained from I. viscosa leaves was evaluated in hypertensive L-NAME rats. Systolic blood pressure (SBP) was measured using a non-invasive indirect tail-cuff plethysmographic method. Four groups of rats were used: a control group; a hypertensive group treated with L-NAME (32mg/kg/day); a positive control group treated with L-NAME plus enalapril (15mg/kg/day) as a reference antihypertensive agent; and a group treated with L-NAME plus MeOH-extract (40mg/kg/day). METHODS Treatment with L-NAME alone caused a progressive increase in SBP. After 4 weeks, the value of SBP reached 160±2mmHg which shows the installation of hypertension. Enalapril prevented the increase in SBP, which remained normal at 123±1mmHg after 4 weeks of treatment. The administration of MeOH-extract along with L-NAME prevented the increase in SBP as well, which remained constant at 115±1mmHg after 4 weeks of treatment. In ex-vivo models, MeOH-extract produced a relaxation of pre-contracted ring aorta (54 ± 2% of relaxation at 3g/L). But, when the rings were denuded, MeOH-extract failed to relax pre-contracted rings of aorta. Phytochemical study of I. viscosa MeOH-extract revealed the presence of phenolic compounds, such as cynarin and chlorogenic acid. RESULTS The present results suggest that I. viscosa MeOH-extract has an antihypertensive, predominantly mediated by an endothelium-dependent vasodilatory effect. Cynarin and chlorogenic acid, which have a strong vasorelaxant effect may be involved in the antihypertensive effect of the plant extract. The bioinformatic POM analysis confirms the therapeutic potential of cynarin and chlorogenic acids as inhibitors of various biotargets. Based on the results, the coordination of these phytochemicals with calcium and transition metals should be studied, for better scope at antihypertensive drug development.

Muscle relaxant activities of pistagremic acid isolated from Pistacia integerrima

Abstract The aim of the current work was to explore the muscle relaxant effect of pistagremic acid (PA) isolated from Pistacia integerrima in various animal paradigms. In a rotarod test, PA caused a significant (p<0.05) muscle relaxant potential in a dose-dependent manner. When studied in the inclined plane test, pretreatment with PA (5 and 10 mg/kg) caused promising activity (p<0.05) after treatment for 30, 60 and 90 min. The muscle relaxant potential of PA was strongly complimented by the traction and chimney tests, showing a dominant effect after 60 min of treatment. In conclusion, PA possesses strong muscle relaxant activity in various animal-based models.

A New Sucrase Enzyme Inhibitor from Azadirachta indica.

Background: Sucrase enzyme inhibitor considered as an oral anti-diabetic therapy that delays the absorption of eaten carbohydrates, reducing the postprandial glucose and insulin peaks to reach normoglycemia. Materials and Methods: Chromatographic fractionation of the hydroalcoholic extract of leaves of Azadirachta indica growing in KSA, followed by in-vitro assay of sucrase enzyme inhibition activity. Results: This investigation led to the isolation of a new remarkable sucrase enzyme inhibitor; 4`-methyl Quercetin-7-O-β-D-glucuronopyranoside (1) alongside with four known compounds; 2,3-hexahydroxydiphenoyl-(α/β)-D-4C1 -glucopyranose (2), Avicularin (3), Castalagin (4) and Quercetin-3-O-glucoside (5). The structure of the new compound (1) was elucidated on the basis of its spectral data, including ESI-MS, UV, 1H NMR, 13C NMR, 1H- 1H COSY, HSQC, NOESY and HMBC. Conclusion: Under the assay conditions, hydroalcoholic extract of A. indica and compounds 1-5 exhibited significant sucrase enzyme inhibitory activity.