Article

PASS-assisted exploration of new therapeutic potential of natural products

Medicinal Chemistry Research (Impact Factor: 1.61). 04/2011; 20(9):1509-1514. DOI: 10.1007/s00044-010-9398-y

ABSTRACT The use of drug substances derived from plants, fungi, bacteria, and marine organisms are “Mother Nature Gift” for diseases
of mankind. Many of these are discovered serendipitously and have a long tradition in medicine. Till date, the use of natural
products, their semisynthetic and synthetic derivatives have been mostly confined to their ethnic use. But it has been well
known that each substance has a wide spectrum of biological activities as evident from some new uses of many old drugs. PASS
(Prediction of Activity Spectra for Substances) has been employed as a strong potential tool to predict the biological activity
spectrum of synthetic substances for the discovery of new drugs. But the potential of PASS to predict the biological activity
spectra of natural products is still underestimated. The present study was therefore undertaken to investigate and correlate
the biological activity spectrum of the main phytoconstituent of some selected Indian medicinal plants with their reported
biological activities in order to evaluate the applicability of PASS. Further, the unexplored but PASS-predicted activities
having good activity score (Pa>0.7) for particular structure were listed as hidden potential of the plant.

KeywordsAyurveda–Biological activity spectrum–Herbal drugs–Natural products–PASS

0 Bookmarks
 · 
160 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bacterial secondary metabolites display diverse biological activities, thus having potential as pharmacological agents. Although most of these compounds are discovered by random screening, it is possible to predict and re-design their structures based on the information on their biosynthetic pathways. Biosynthesis of macrolides, governed by modular polyketide synthases (PKS), obeys certain rules, which can be simulated in silico. PKS mode of action theoretically allows for a huge number of macrolides to be produced upon combinatorial manipulation. Since engineering of all possible PKS variants is practically unfeasible, we created Biogenerator software, which simulates manipulation of PKS and generates virtual libraries of macrolides. These libraries can be screened by computer-aided prediction of biological activities, as exemplified by analysis of erythromycin and macrolactin libraries. This approach allows rational selection of macrolides with desired biological activities and provides instructions regarding the composition of the PKS gene clusters necessary for microbial production of such molecules.
    Journal of Medicinal Chemistry 04/2006; 49(6):2077-87. · 5.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dietary constituents (e.g., in grapefruit juice; NaCl) and phytochemicals (e.g., St. John's wort) are important agents modifying drug metabolism and transport and thereby contribute to interindividual variability in drug disposition. Most of these drug-food interactions are due to induction or inhibition of P-glycoprotein and/or CYP3A4. Preliminary data indicate that piperine, a major component of black pepper, inhibits drug-metabolizing enzymes in rodents and increases plasma concentrations of several drugs, including P-glycoprotein substrates (phenytoin and rifampin) in humans. However, there are no direct data whether piperine is an inhibitor of human P-glycoprotein and/or CYP3A4. We therefore investigated the influence of piperine on P-glycoprotein-mediated, polarized transport of digoxin and cyclosporine in monolayers of Caco-2 cells. Moreover, by using human liver microsomes we determined the effect of piperine on CYP3A4-mediated formation of the verapamil metabolites D-617 and norverapamil. Piperine inhibited digoxin and cyclosporine A transport in Caco-2 cells with IC(50) values of 15.5 and 74.1 microM, respectively. CYP3A4-catalyzed formation of D-617 and norverapamil was inhibited in a mixed fashion, with K(i) values of 36 +/- 8 (liver 1)/49 +/- 6 (liver 2) and 44 +/- 10 (liver 1)/77 +/- 10 microM (liver 2), respectively. In summary, we showed that piperine inhibits both the drug transporter P-glycoprotein and the major drug-metabolizing enzyme CYP3A4. Because both proteins are expressed in enterocytes and hepatocytes and contribute to a major extent to first-pass elimination of many drugs, our data indicate that dietary piperine could affect plasma concentrations of P-glycoprotein and CYP3A4 substrates in humans, in particular if these drugs are administered orally.
    Journal of Pharmacology and Experimental Therapeutics 09/2002; 302(2):645-50. · 3.89 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The inhibitory effects of four acidamides, piperine, pipernonaline, piperoctadecalidine, and piperlongumine, isolated from the fruits of Piper longum L. on washed rabbit platelet aggregation were examined. All of the four tested acidamides showed dose-dependent inhibitory activities on washed rabbit platelet aggregation induced by collagen, arachidonic acid (AA), and platelet-activating factor (PAF), except for that induced by thrombin. Piperlongumine, in particular, showed stronger inhibitory effects than other acidamides to rabbit platelet aggregation induced by collagen, AA and PAF.
    Phytomedicine 01/2008; 14(12):853-5. · 2.97 Impact Factor

Full-text (2 Sources)

View
126 Downloads
Available from
May 30, 2014