Insilico studies of organosulfur-functional active compounds in garlic

BioFactors

Volumn 36, Issue 4, 2010, Pages 297-311

  Singh, Yogendra P ^a   Singh, Ram A ^b  

^a Govt Women's Polytechnic College   (India)

^b DR H S GOUR UNIVERSITY   (India)

Author keywords

Anticancer; Antioxidant; Garlic; Nutrition; Organosulfur compounds

Indexed keywords

3 VINYL 4H 1,2 DITHIIN; 3 VINYL 6H 1,2 DITHIIN; 3 VINYL 6H 1,3 DITHIIN; ALLICIN; ALLIIN; ALLIIN LYASE; ALLYLMETHANE SULFINATE; ALLYLMETHYLTHIOSULFINATE; ANTINEOPLASTIC AGENT; ANTIOXIDANT; DIALLYLDISULFIDE; DIALLYLTETRASULFIDE; DIALLYLTRISULFIDE; DIMETHYL DISULFIDE; DIMETHYL SULFIDE; DIPROPYL DISULFIDE; DIPROPYL SULFIDE; GLYCOPROTEIN P; METHYLALLYLTRISULFIDE; METHYLCYSTEINE SULFOXIDE; METHYLMETHANE SULFINATE; METHYLPROPYLDISULFIDE; ORGANOSULFUR DERIVATIVE; PROPYLCYSTEINE SULFOXIDE; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; AQUEOUS SOLUTION; ARTICLE; BACTERIAL STRAIN; BLOOD BRAIN BARRIER; CHEMICAL STRUCTURE; COMPUTER MODEL; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG PENETRATION; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG SOLUBILITY; DRUG TRANSPORT; ESCHERICHIA COLI; GARLIC; GENOTOXICITY; HYDROGEN BOND; IC 50; LD 50; LIPOPHILICITY; MOLECULAR MODEL; MOLECULAR WEIGHT; NONHUMAN; PARTITION COEFFICIENT; PRIORITY JOURNAL; PROTEIN EXPRESSION; QUANTITATIVE STRUCTURE ACTIVITY RELATION; QUANTUM CHEMISTRY; REVERTANT; SALMONELLA TYPHIMURIUM; THEORETICAL STUDY; TOXICITY TESTING;

ANTICARCINOGENIC AGENTS; GARLIC; P-GLYCOPROTEIN; PHYTOTHERAPY; PLANT EXTRACTS; SULFUR COMPOUNDS;

ALLIUM SATIVUM; ANIMALIA;

EID: 78149476357     PISSN: 09516433     EISSN: 18728081     Source Type: Journal    
DOI: 10.1002/biof.102     Document Type: Article

References (85)

1. Kawakishi, S. and Morimitsu, Y. (1994) Sulfur chemistry of onion and inhibitory factors of the arachidonic acid cascade. In Food Phytochemicals for Cancer Prevention I, ACS Symposium Series, 546 (Huang, M.-T., Osawa, T., Ho, C.-T., and Rosen, R. T., eds.). pp. 120-127, American Chemical Society, ISBN13: 978084122768.
2. Milner, J. A. (2001) A historical perspective on garlic and cancer. J. Nutr. 131, 1027S-1031S.
3. Oi, Y., Kawada, T., Kitamura, K., Oyama, F., Nitta, M., Kominato, Y., Nishimura, S., and Iwai, K. (1995) Garlic supplementation enhances norepinephrine secretion, growth of brown adipose tissue, and triglyceride catabolism in rats. J. Nutr. Biochem. 6, 250-255.
4. Sumiyoshi, H. and Wargovich, M. J. (1990) Chemoprevention of 1, 2-dimethylhydrazine-induced colon cancer in mice by naturally occurring organosulfur compounds. Cancer Res. 50, 5084-5087.
5. Block, E. (1985) The chemistry of garlic and onions: a number of curious sulphur compounds underlie the odor of garlic and the crying brought on by slicing an onion. The compounds also account for medical properties long ascribed to garlic and onions. Sci Am. 252, 114-119.
6. Rahman, M. S. (2007) Allicin and other functional active components in garlic: health benefits and bioavailability. Int. J. Food Properties 10, 245-268.
7. Chi, M. S. (1982) Effects of garlic products on lipid metabolism in cholesterol fed rats. Proc. Soc. Exp. Biol. Med. 171, 174-178.
8. Thomson, M. and Ali, M. (2003) Garlic [Allium sativum]: a review of its potential use as an anti-cancer agent. Curr. Cancer Drug Targets 3, 67-81
9. Nobili, S., Lippi, D., Witort, E., and Mini, E. (2009) Natural compounds for cancer treatment and prevention. Pharmacol. Res. 59, 365-378.
10. Wave Function, Inc. (2008) Spartan' 08 for Medicinal Chemistry. Wave Function, Inc., Irvine, CA.
11. Becke, A. D. (1993) Density-functional thermochemistry. III. The role of exact exchange. J. Chem. Phys. 98, 5648-5652.
12. Here, W. J., Random, L., Schlyer, P. R. V., and Pople, J. A. (1989) Ab Initio Molecular-Orbital Theory. Wiley, New York.
13. Advanced Chemistry Development (2006). Advanced Chemistry Development (ACD), Toronto, Ontario, Canada.
14. Molinspiration Cheminformatics. Available at: Accessed: October 2009 to March 2010.
15. Molsoft L.L.C. Available at:
16. SPARC, University of Georgia, Athens, GA. Available at:
17. Hypercube Inc. (2002) Hyperchem Package 7 for molecular modeling. Hypercube Inc., FL.
18. Allinger, N. L. (1977) Conformational analysis 130. MM2. A hydrocarbon force field utilizing V1 and V2 torsional terms. J. Am. Chem. Soc. 99, 8127-8134.
19. Amagese, H. (2006) Clarifying the real bioactive constituents of garlic. J. Nutr. 136, 716s-725s.
20. Powolny, A. A. and Singh, S. V. (2008) Multitargeted prevention and therapy of cancer by diallyl trisulfide and related Allium vegetable-derived organosulfur compounds. Cancer Lett. 269, 305-314.
21. Lipinski, C. A., Lombardo, F., Dominy, B. W., and Feeney, P. J. (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 46, 3-26.
22. Refsgaard, H. H. F., Jensen, B. F., Brockhoff, P. B., Padkj'ær, S. B., Guldbrandt, M., and Christensen, M. S. (2005) In silico prediction of membrane permeability from calculated molecular parameters. J. Med. Chem. 48, 805-811.
23. Gnewuch, T. C. and Sosnovsky, G. (2002) Critical appraisals of approaches for predictive designs in anticancer drugs. Cell. Mol. Life Sci. 59, 959-1023.
24. Jepson, G. W., Black, R. K., Mccafferty, J. D., Mahle, A, D., and Gearhart, J. M. (1993) A partition coefficient determination method for nonvolatile chemicals in biological tissues. Toxicol. Sci. 22, 519-524.
25. Nienke de Vries, A., Beijnen, J. H., Boogerd, W., and Tellingen, O. V. (2006) Blood-brain barrier and chemotherapeutic treatment of brain tumors. Future Drugs 6, 1199-1209.
26. Derks, E., Pastor, M. S. S., and Buydens, L. M. C. (1995) Bioavailability prediction based on molecular structure for a diverse series of drugs. Chem. Intell. Lab. Syst. 28, 49-60.
27. Dunn, J. W., III, Koehler, M. G., and Grigoras, S. (1987) The role of solvent-accessible surface area in determining partition coefficients. J. Med. Chem. 30, 1121-1126.
28. Joseph, V. T., Desmond, M, J., and Agatonovic-Kustrin, S. (2004) Bioavailability prediction based on molecular structure for a diverse series of drugs. Pharm Res. 21, 68-82.
29. Ajay, Bemis, G. W., and Murcko, M. A. (1999) Designing libraries with CNS activity. J. Med. Chem. 42, 4942-4951.
30. Veber, D. F., Josehn, S. R., Cheng, H.-Y., Smith, B. R., Ward, W. K., and Kopple, K. D. (2002) Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem. 45, 2615-2623.
31. Lobell, M. (2006) In silico ADMET traffic lights as a tool for the prioritization of HTS hits. ChemMedChem. 1, 1229-1236.
32. Norinder, U. and Haeberlein, M. (2002) Computational approaches to the prediction of the blood-brain distribution. Adv. Drug Deliv. Rev. 54, 291-313.
33. Van de Waterbeemd, H., Camenisch, G., Folkers, G., Chretien, J. R., Raevsky, O. A. (1998) Estimation of blood-brain barrier crossing of drugs using molecular size and shape, and H-bonding descriptors. J. Drug Target 6, 151-165.
34. Sveigaard, H. H. and Dalgaard, L. (2000) Evaluation of blood-brain penetration measured by in vivo microdialysis. Pharm. Res. 17, 70-76.
35. Clark, E. D. and Pickett, S. D. (2000) Computational prediction for the prediction of 'drug likeness'. Drug Discov. Today 5, 49-58.
36. Iyer, M., Mishra, R., Yi, H., and Hopfinger, A. J. (2004) Predicting blood-brain barrier partitioning of organic molecules using membrane-interaction QSAR analysis. Pharm. Res. 2, 1611-1621.
37. Clark, D. E. (1999) Rapid calculation of polar molecular surface area. J. Pharm. Sci. 88, 815-821.
38. Abrahm, M. H. (1997) On partition of ampholytes: application to BBB. J. Pharm. Sci. 86, 310-315.
39. Smith, D. A., Waterbeemed, H., and Walker, D. K. (2006)Pharmacokinetics and Metabolism in Drug Designing, 2nd edn. Wiley-VCH, Verlag GmbH, Weinheim.
40. Yalkowsky, S. H. (1999) Solubility and Solubilization in Aqueous Media. Oxford University Press, Oxford.
41. Jorgensen, W. L. (2007) The many roles of computation in drug discovery. Science 303, 1813-1818.
42. Smith, Q. R., Fisher, C., and Allen, D. D. (2001) Blood-brain barrier: drug delivery and brain physiology, In Proceedings of the 44th OHOLO Conference on Blood-Brain Barrier, Israel. pp. 311-321, Kluwer Academic/Plenum Publishers, New York.
43. Gao, H., Shanmugasundaram, V., and Lee, P. (2002) Estimation of aqueous solubility of organic compounds with QSPR approach. Pharm. Res. 19, 497-503.
44. Klamt, A. and Smith, B. J. (2008) Challenge of Drug Solubility, Molecular Drug Properties, Measurement and Prediction; Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 283 p.
45. Asperen, J. V., Tellingen, O. V., Schinkel, A. H., and Bijnen, J. H. (1999) Comparative pharmacokinetics of vinblastine after a 96-hour continuous infusion in wild-type mice and mice lacking mdr1a P glycoprotein. J Pharmacol. Exp. Ther., 289, 1.
46. Thiebaut, F., Tsuruo, T., Hamada, H., Gottesman, M. M., Pastan, I., and Willingham, M. C. (1987) Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc. Natl. Acad. Sci. USA 84, 7735-7738.
47. Gatlik-Landwojtowicz, E., Aänismaa, P., and Seelig, A. (2006) Quantification and characterization of P-glycoprotein-substrate interactions. Biochemistry 45, 3020-3032.
48. Barecki-Roach, M., Wang, E. R.-J. I. A., and Johnson, W. W. (2003) Many P-glycoprotein substrates do not inhibit the transport process across cell membranes. Xenobiotica 33, 131-140.
49. Pharma Algorithms. Available at:
50. Kariv, I., Cao, H., and Oldenburg, K. R. (2001) Development of a high throughput equilibrium dialysis method. J. Pharm. Sci. 90, 580-587.
51. Banker, M. J., Clark, T. H., and Williams, J. A. (2003) Development and validation of a 96-well equilibrium dialysis apparatus for measuring plasma protein binding. J. Pharm. Sci. 92, 967-974.
52. Blodgett, J. and Lynch, J. (2003) MultiScreen filter assembly with ultracel-PPB membrane. Millipore Application Note AN1732EN00. pp. 5-11, Millipore Corporation, 290 Concord Road, Billerica, MA.
53. Tiwari, V. and Pande, R. (2006) Molecular descriptors of N-arylhydroxamic acids: a tool in drug design. Chem. Biol. Drug Des. 68, 225-228.
54. Fung, E. N., Chen, Y.-H., and Lau, Y. Y. (2003) Semi-automatic high-throughput determination of plasma protein binding using a 96-well plate filtrate assembly and fast liquid chromatography-tandem mass spectrometry. J. Chromatogr. B 795, 187-194.
55. Cheng, Y., Ho, E., Subramanyam, B., and Tseng, J.-L. (2004) Measurements of drug-protein binding by using immobilized human serum albumin liquid chromatography-mass spectrometry. J. Chromatogr. B 809, 67-73.
56. Musteata, F. M., Pawliszyn, J., Mark, G. Q., Wu, J.-T., Gerald, T. M. (2006) Determination of drug plasma protein binding by solid phase microextraction. J Pharm Sci. 95, 1712-1722.
57. Lombardo, F. (2004) Prediction of human volume of distribution values for neutral and basic drugs. J. Med. Chem. 47, 1242-1250.
58. Accelrys, Inc. Available at:
59. Mager, D. E. (2006) Quantitative structure-pharmacokinetic/pharmacodynamic relationships. Adv Drug Deliv Rev. 58, 326-1356.
60. Mayer, J. M., Hall, S. D., and Rowland, M. (1988) Relationship between lipophilicity and tubular reabsorption for a series of 5-alkyl-5-ethylbarbituric acids in the isolated perfused rat kidney preparation. J. Pharm. Sci. 77, 359-364.
61. Martinez, M. N. and Amidon, G. L. (2002) A mechanistic approach to understanding the factors affecting drug absorption: a review of fundamentals. J. Clin. Pharmacol. 42, 620-643.
62. Cummins, C. L., Jacobsen, W., and Benet, L. Z. (2002) Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4. J. Pharmacol. Exp. Ther. 300, 1036-1045.
63. Wu, C. Y. and Benet, L. Z. (2005) Predicting drug disposition via applications of BCS: transport/absorption/elimination/interplay and development of a biopharmaceutics drug disposition classification system. Pharma. Res. 22, 11-23.
64. Watari, N., Sugiyama, Y., Kaneniwa, N., and Hiura, M. (1998) Prediction of hepatic first-pass metabolism and plasma levels following intravenous and oral administration of barbiturates in the rabbit based on quantitative structure-pharmacokinetic relationships. J. Pharmacokinet. Biopharm. 16, 279-301.
65. Johnson, K. and Swindell, A. (1996) Guidance in the setting of drug particle size specifications to minimize variability in absorption. Pharm. Res. 13, 1795-1798.
66. Curatolo, W. (1998) Physical chemical properties of oral drug candidates in the discovery and exploratory development settings. Pharm. Sci. Technol. Today, 1, 387-393.
67. Abraham, M. H., Zhao, Y. H., Le, J., Hersey, A., Eddershaw, P. J., Luscombe, C. N., Butina, D., Beck, G., Sherbome, B., Cooper, I., and Platts, J. A. (2001) Evaluation of human intestinal absorption data and subsequent derivation of a WSAR with Abraham descriptors. J. Pharm. Sci. 90, 749-784.
68. Eddershaw, P. J. and Dickens, M. (1999) Advances in vitro drug metabolism screening. Pharm. Sci. Technol. Today, 2, 13-19.
69. Navia, A. M. and Chaturvedi, P. R. (1996) Design principles for orally bioavailable drugs. Drug Discov. Today 1, 179-189.
70. Chaturveldi, P. R., Deker, C. J., and Odinecs, A. (2001) Prediction of pharmacokinetic properties using experimental approaches during early drug discovery. Curr. Opin. Chem. Biol. 5, 452-463.
71. Artursson, P. and Karlsson, J. (1991) Correlation between oral drug permeability coefficients in human intestinal epithalial (Caco-2 cells). Biochem. Biophys. Res. Commun. 175, 880-885.
72. Delie, F. and Rubas, W. (1997) A human colonic cell line sharing similarities with enterocytes as a model. Crit. Rev. Ther. Drug Carrier Syst. 14, 221-286.
73. Winiwarter, S. (1998) Correlation of human jejuna permeability of drugs with experimentally and theoretically derived parameters. J. Med. Chem. 41, 4939-4949.
74. Charton, M. and Charton, B. L. (1982) The structural dependence of amino acid hydrophobicity parameters. J. Theor. Biol. 99, 629-644.
75. Kawasaki, S., Miyake, C., Kohchi, T., Fujii, S., Uchida, M., and Yokota, A. (2000) Responses of wild watermelon to drought stress. Plant Cell Physiol. 41, 864-873.
76. Hansc, C. and Clayton, J. M. (1973) Lipophilic character and biological activity of drugs. J. Pharm. Sci. 62, 1-21.
77. Gosselin, R. E., Smith, R. P., and Hodge, H. C. (1984) Clinical Toxicology of Commercial Products, 5th edn. Williams and Wilkins, Baltimore, MD.
78. Guha, R. and Schürer, S. C. (2008) Utilizing high throughput screening data for predictive toxicology models: protocols and application to MLSCN assays. J. Comput-Aided Mol. Des. 22, 367-384.
79. Quantum Pharmaceuticals. Available at: www.drugdiscoverywizzards.com.
80. Contrera, J. F., Matthews, E. J. Kruhlak, L. N., and Benz, R. D. (2004) A comprehensive model for reproductive and developmental toxicity hazard identification. I. Development of a weight of evidence QSAR database. Regul. Toxicol. Pharmacol. 40, 185-206.
81. Didziapetris, R., Reynolds, D. P., Japertas, P., Zmuidinavicius, D., and Petrauskas, A. (2006) Computational methods for analysis of high-throughput screening data. Curr. Comput-Aided Drug Des. 2, 1-19.
82. Rahman, M. S. (2007) Allicin and other functional active component in garlic. Int. J. Food Properties 10, 245-268.
83. Patrick, W. and Murcko, M. A. (2002) Prediction of drug likeness. Adv. Drug Deliv. Rev. 54, 255-271.
84. Muegge, I., Heald, S. L., and Brittelli, D. (2001) Simple selection criteria for drug-like chemical matter. J. Med. Chem. 44, 1841-1846.
85. Turner, J. V., Glass, B. D., and Agatonovic-Kustrin, S. (2003) Prediction of drug bioavailability based on molecular structure. Anal. Chim. Acta 485, 89-102.