Two Novel Flavone C-Glycosides Isolated From Afrocarpus Gracilior: Pom Analyses And In Vitro Cytotoxic Activity Aganist Hepatocellular Carcinoma

Objective: Cancer is considered as one of the top reasons of death and the number of cases increasing gradually. Cancer is severe clinical difficulty to the health caution system. This study explored two novel polyphenols of Afrocarpus gracilior Pilger growing in Egypt and evaluated their cytotoxic activity. Methods: Methanolic (80%) extract of the leaves of A. gracilior was subjected to column chromatography; the chemical structures of the isolated compounds were established by advanced spectral techniques: UV, 1H, 13C NMR, two dimensional NMR (2D NMR) and electron spray ionization mass spectroscopy (ESI-MS). Compounds 1 and 2 were studied for their cytotoxic activity against hepatocellular carcinoma (Hep-G2) using sulforhodamine B (SRB) assay. Furthermore the pharmacokinetics profiles of these molecules were accessed by employing Petra/Osiris/Molinspiration (POM) analyses. Results: Two novel C-flavonoid glycosides were isolated [1: Apigenin 8-C-β-D-glucopyranosyl-(1```→4``)-O-β-D-glucopyranoside] and [2: 7-O methyl-luteolin 8-C-β-glucopyranosyl-(1```→4``)-O-β-D-glucopyranoside]. They exhibited significant cytotoxic activity (IC50 = 9.02 and 15.61 µg/ml, respectively) against Hep-G2 cells. The POM analyses revealed that the activity of these two compounds depends on the presence of glucosyl and alkyl groups at the internal and terminal atmosphere of the compounds. Conclusion: These findings demonstrated that the leaves of A. gracilior contain a series of bioactive polyphenolic compounds with significant cytotoxic properties against hepatocellular carcinoma and may be used as alternative anticancer agents for doxorubicin. On the basis of POM calculations, it will be interesting to develop some alternative flavones because the deglucosylated derivatives have a better drug score than parent molecules. This preliminary study will be extended to other strains of cancer.

An In-Silico Evaluation of Some Novel Curcumin Derivatives for Antibacterial Activity Against Methicillin Resistant Staphylococcus Aureus.

The multiple drug resistance in MRSA (Methicillin resistant Staphylococcus aureus) has become a major clinical problem worldwide. Methicillin resistance (mediated by PBP2a protein) is a serious issue limiting treatment options and necessitating the search of newer safe and effective alternative treatment regimens. Aim of the present study was to evaluate the potential of the plant product ‘Curcumin’ and its derivatives as effective antibacterial agents by means of insilico based studies. Computer aided drug designing is an initial platform helpful to screen novel inhibitors and has tremendous application in the development of new drugs. In the present study a series of 16 derivatives of curcumin were constructed and optimized using chemsketch software.Molecular docking was performed using the GOLD (Genetic Optimization of Ligand Docking) software which is based on genetic algorithm (GA), to study the binding orientation of these derivatives into the PBP2a structure. Derivative 10 (1E,6E)-1,7-bis(3- hydroperoxy-4-hydroxyphenyl)hepta-1,6-diene-3,5-dione) showed best docking fitness value compared to other derivatives(including Curcumin). The molecular, physicochemical, and biological properties were calculated (through molinspiration cheminformatics software) for compounds showing the best docking scores. These compounds were further subjected to toxicity predictions using the Osiris software.

Virtual Screening of Molecular Properties and Bioactivity Score of Boswellic Acid Derivatives in Search of Potent Anti-Inflammatory Lead Molecule.

The aim of this study was to examine correlation between anti-inflammatory activity and molecular properties of the Boswellic acid derivatives in search of a lead compound through molinspiration cheminformatics software. Twelve naturally occurring and semisynthetic derivatives of Boswellic acid were selected for bioactivity prediction and drug likeness score on the basis of Lipinski’s rule. Aceclofenac and Hydrocortisone (cortisol) were used as reference standard for comparing the molecular properties and bioactivity score. None of the compounds fulfilled Lipinski’s rule as their Milog P score was above 5 suggesting these compounds are highly lipophilic with very poor aqueous solubility. All the screened compounds had minimum one and maximum three violations of Lipinski rule. BA and its derivatives showed good bioactivity score for drug targets including nuclear receptor ligand, protease inhibitor and enzyme inhibition and thus expected to have excellent pharmacological activity in vivo. The results of this study justify their topical application in arthritic conditions but some structural modifications in order to make the compound more polar will definitely improve oral bioavailability and thus the usefulness and therapeutic efficacy of BAs. Among all the boswellic acid derivatives, only compound number 2 is predicted to be orally active and is considered as a potential candidate for the further research as its bioactivity score due to high affinity for various drug targets was better than the standard (Cortisol and Aceclofenac) as well as among other tested compounds.

Microwave assisted synthesis and biological evaluation of 2-aryl/heteryl-3-aryloxy/heteryloxy-4h-chromones (4-oxo-2-aryl/heteryl-4h-chromen-3-yl-carboxylate).

2-Aryl/heteryl-3-aryloxy/heteryloxy-4H-chromones 5 have been synthesized through a series of reactions starting from phenols under microwave irradiation. This process is an effective alternative to the traditional thermal heating method. The yields are excellent and the reaction time is in a few minutes. These compounds have been characterized on the basis of IR, 1H NMR, 13C NMR and Mass spectrometry and evaluated for antibacterial activity.