{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T09:56:00Z","timestamp":1723110960296},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2013,1,21]],"date-time":"2013-01-21T00:00:00Z","timestamp":1358726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Cheminform"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>In order to better understand the structural features of natural compounds from traditional Chinese medicines, the scaffold architectures of drug-like compounds in MACCS-II Drug Data Report (MDDR), non-drug-like compounds in Available Chemical Directory (ACD), and natural compounds in Traditional Chinese Medicine Compound Database (TCMCD) were explored and compared.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>First, the different scaffolds were extracted from ACD, MDDR and TCMCD by using three scaffold representations, including Murcko frameworks, Scaffold Tree, and ring systems with different complexity and side chains. Then, by examining the accumulative frequency of the scaffolds in each dataset, we observed that the Level 1 scaffolds of the Scaffold Tree offer advantages over the other scaffold architectures to represent the scaffold diversity of the compound libraries. By comparing the similarity of the scaffold architectures presented in MDDR, ACD and TCMCD, structural overlaps were observed not only between MDDR and TCMCD but also between MDDR and ACD. Finally, Tree Maps were used to cluster the Level 1 scaffolds of the Scaffold Tree and visualize the scaffold space of the three datasets.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>The analysis of the scaffold architectures of MDDR, ACD and TCMCD shows that, on average, drug-like molecules in MDDR have the highest diversity while natural compounds in TCMCD have the highest complexity. According to the Tree Maps, it can be observed that the Level 1 scaffolds present in MDDR have higher diversity than those presented in TCMCD and ACD. However, some representative scaffolds in MDDR with high frequency show structural similarities to those in TCMCD and ACD, suggesting that some scaffolds in TCMCD and ACD may be potentially drug-like fragments for fragment-based and <jats:italic>de novo<\/jats:italic> drug design.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1758-2946-5-5","type":"journal-article","created":{"date-parts":[[2013,1,21]],"date-time":"2013-01-21T11:14:08Z","timestamp":1358766848000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Drug-likeness analysis of traditional Chinese medicines: 2. Characterization of scaffold architectures for drug-like compounds, non-drug-like compounds, and natural compounds from traditional Chinese medicines"],"prefix":"10.1186","volume":"5","author":[{"given":"Sheng","family":"Tian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youyong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junmei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingjun","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2013,1,21]]},"reference":[{"key":"367_CR1","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1016\/S1359-6446(99)01405-1","volume":"4","author":"RN Lawrence","year":"1999","unstructured":"Lawrence RN: Rediscovering natural product biodiversity. Drug Discov Today. 1999, 4: 449-451. 10.1016\/S1359-6446(99)01405-1.","journal-title":"Drug Discov Today"},{"key":"367_CR2","doi-asserted-by":"publisher","first-page":"1022","DOI":"10.1021\/np030096l","volume":"66","author":"DJ Newman","year":"2003","unstructured":"Newman DJ, Cragg GM, Snader KM: Natural products as sources of new drugs over the period 1981\u20132002. J Nat Prod. 2003, 66: 1022-1037. 10.1021\/np030096l.","journal-title":"J Nat Prod"},{"key":"367_CR3","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.cbpa.2004.04.010","volume":"8","author":"AM Boldi","year":"2004","unstructured":"Boldi AM: Libraries from natural product-like scaffolds. Curr Opin Chem Biol. 2004, 8: 281-286. 10.1016\/j.cbpa.2004.04.010.","journal-title":"Curr Opin Chem Biol"},{"key":"367_CR4","doi-asserted-by":"publisher","first-page":"355","DOI":"10.2533\/chimia.2007.355","volume":"61","author":"S Wetzel","year":"2007","unstructured":"Wetzel S, Schuffenhauer A, Roggo S, Ertl P, Waldmann H: Cheminformatic analysis of natural products and their chemical space. Chimia. 2007, 61: 355-360. 10.2533\/chimia.2007.355.","journal-title":"Chimia"},{"key":"367_CR5","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1021\/np068054v","volume":"70","author":"DJ Newman","year":"2007","unstructured":"Newman DJ, Cragg GM: Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007, 70: 461-477. 10.1021\/np068054v.","journal-title":"J Nat Prod"},{"key":"367_CR6","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.2174\/0929867023368773","volume":"9","author":"R Breinbauer","year":"2002","unstructured":"Breinbauer R, Manger M, Scheck M, Waldmann H: Natural product guided compound library development. Curr Med Chem. 2002, 9: 2129-2145. 10.2174\/0929867023368773.","journal-title":"Curr Med Chem"},{"key":"367_CR7","first-page":"115","volume":"1","author":"K Grabowski","year":"2007","unstructured":"Grabowski K, Schneider G: Properties and architecture of drugs and natural products revisited. Current Chemical Biology. 2007, 1: 115-127.","journal-title":"Current Chemical Biology"},{"key":"367_CR8","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1021\/ci050352v","volume":"46","author":"M Krier","year":"2006","unstructured":"Krier M, Bret G, Rognan D: Assessing the scaffold diversity of screening libraries. J Chem Inf Model. 2006, 46: 512-524. 10.1021\/ci050352v.","journal-title":"J Chem Inf Model"},{"key":"367_CR9","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1021\/cc000097l","volume":"3","author":"ML Lee","year":"2001","unstructured":"Lee ML, Schneider G: Scaffold architecture and pharmacophoric properties of natural products and trade drugs: application in the design of natural product-based combinatorial libraries. J Comb Chem. 2001, 3: 284-289. 10.1021\/cc000097l.","journal-title":"J Comb Chem"},{"key":"367_CR10","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1021\/jm00120a002","volume":"31","author":"BE Evans","year":"1988","unstructured":"Evans BE, Rittle KE, Bock MG, Dipardo RM, Freidinger RM, Whitter WL, Lundell GF, Veber DF, Anderson PS, Chang RSL, Lotti VJ, Cerino DJ, Chen TB, Kling PJ, Kunkel KA, Springer JP, Hirshfield J: Methods for drug discovery - development of potent, selective, orally effective cholecystokinin antagonists. J Med Chem. 1988, 31: 2235-2246. 10.1021\/jm00120a002.","journal-title":"J Med Chem"},{"key":"367_CR11","doi-asserted-by":"publisher","first-page":"4568","DOI":"10.1021\/jm060217p","volume":"49","author":"P Ertl","year":"2006","unstructured":"Ertl P, Jelfs S, Muhlbacher J, Schuffenhauer A, Selzer P: Quest for the rings. In silico exploration of ring universe to identify novel bioactive heteroaromatic scaffolds. J Med Chem. 2006, 49: 4568-4573. 10.1021\/jm060217p.","journal-title":"J Med Chem"},{"key":"367_CR12","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.ddtec.2004.10.009","volume":"1","author":"HJ Bohm","year":"2004","unstructured":"Bohm HJ, Flohr A, Stahl M: Scaffold hopping. Drug discov today: Technologies. 2004, 1: 217-224.","journal-title":"Drug discov today: Technologies"},{"key":"367_CR13","doi-asserted-by":"publisher","first-page":"2887","DOI":"10.1021\/jm9602928","volume":"39","author":"GW Bemis","year":"1996","unstructured":"Bemis GW, Murcko MA: The properties of known drugs.1. Molecular frameworks. J Med Chem. 1996, 39: 2887-2893. 10.1021\/jm9602928.","journal-title":"J Med Chem"},{"key":"367_CR14","doi-asserted-by":"publisher","first-page":"5095","DOI":"10.1021\/jm9903996","volume":"42","author":"GW Bemis","year":"1999","unstructured":"Bemis GW, Murcko MA: Properties of known drugs. 2. Side chains. J Med Chem. 1999, 42: 5095-5099. 10.1021\/jm9903996.","journal-title":"J Med Chem"},{"key":"367_CR15","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.jmgm.2004.03.016","volume":"23","author":"HB Broughton","year":"2004","unstructured":"Broughton HB, Watson IA: Selection of heterocycles for drug design. J Mol Graph Model. 2004, 23: 51-58. 10.1016\/j.jmgm.2004.03.016.","journal-title":"J Mol Graph Model"},{"key":"367_CR16","doi-asserted-by":"publisher","first-page":"17272","DOI":"10.1073\/pnas.0503647102","volume":"102","author":"MA Koch","year":"2005","unstructured":"Koch MA, Schuffenhauer A, Scheck M, Wetzel S, Casaulta M, Odermatt A, Ertl P, Waldmann H: Charting biologically relevant chemical space: a structural classification of natural products (SCONP). Proc Natl Acad Sci USA. 2005, 102: 17272-17277. 10.1073\/pnas.0503647102.","journal-title":"Proc Natl Acad Sci USA"},{"key":"367_CR17","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1021\/ci000144x","volume":"41","author":"AH Lipkus","year":"2001","unstructured":"Lipkus AH: Exploring chemical rings in a simple topological-descriptor space. J Chem Inf Comput Sci. 2001, 41: 430-438. 10.1021\/ci000144x.","journal-title":"J Chem Inf Comput Sci"},{"key":"367_CR18","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1021\/ci600338x","volume":"47","author":"A Schuffenhauer","year":"2007","unstructured":"Schuffenhauer A, Ertl P, Roggo S, Wetzel S, Koch MA, Waldmann H: The scaffold tree - Visualization of the scaffold universe by hierarchical scaffold classification. J Chem Inf Model. 2007, 47: 47-58. 10.1021\/ci600338x.","journal-title":"J Chem Inf Model"},{"key":"367_CR19","doi-asserted-by":"publisher","first-page":"5002","DOI":"10.1021\/jm1004495","volume":"53","author":"DK Agrafiotis","year":"2010","unstructured":"Agrafiotis DK, Wiener JJM: Scaffold explorer: an interactive tool for organizing and mining structure-activity data spanning multiple chemotypes. J Med Chem. 2010, 53: 5002-5011. 10.1021\/jm1004495.","journal-title":"J Med Chem"},{"key":"367_CR20","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nchembio.187","volume":"5","author":"S Wetzel","year":"2009","unstructured":"Wetzel S, Klein K, Renner S, Rauh D, Oprea TI, Mutzel P, Waldmann H: Interactive exploration of chemical space with Scaffold Hunter. Nat Chem Biol. 2009, 5: 581-583. 10.1038\/nchembio.187.","journal-title":"Nat Chem Biol"},{"key":"367_CR21","first-page":"55","volume":"50","author":"J Wang","year":"2009","unstructured":"Wang J, Hou T: Drug and drug candidate building block analysis. J Med Chem. 2009, 50: 55-67.","journal-title":"J Med Chem"},{"key":"367_CR22","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1021\/ci010113h","volume":"42","author":"XB Qiao","year":"2002","unstructured":"Qiao XB, Hou TJ, Zhang W, Guo SL, Xu SJ: A 3D structure database of components from Chinese traditional medicinal herbs. J Chem Inf Comput Sci. 2002, 42: 481-489. 10.1021\/ci010113h.","journal-title":"J Chem Inf Comput Sci"},{"key":"367_CR23","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1021\/ci60003a003","volume":"15","author":"WT Wipke","year":"1975","unstructured":"Wipke WT, Dyott TM: Use of ring assemblies in a ring perception algorithm. J Chem Inf Comput Sci. 1975, 15: 140-147. 10.1021\/ci60003a003.","journal-title":"J Chem Inf Comput Sci"},{"key":"367_CR24","first-page":"1788","volume":"59","author":"TJ Hou","year":"2001","unstructured":"Hou TJ, Qiao XB, Xu XJ: Research and development of 3D molecular structure database of traditional Chinese drugs. Acta Chimica Sinica. 2001, 59: 1788-1792.","journal-title":"Acta Chimica Sinica"},{"key":"367_CR25","doi-asserted-by":"publisher","first-page":"497","DOI":"10.2174\/138620709788489082","volume":"12","author":"TJ Hou","year":"2009","unstructured":"Hou TJ, Li YY, Zhang W, Wang JM: Recent Developments of In Silico predictions of intestinal absorption and oral bioavailability. Comb Chem High Throughput Screen. 2009, 12: 497-506. 10.2174\/138620709788489082.","journal-title":"Comb Chem High Throughput Screen"},{"key":"367_CR26","doi-asserted-by":"publisher","first-page":"2653","DOI":"10.2174\/092986706778201558","volume":"13","author":"TJ Hou","year":"2006","unstructured":"Hou TJ, Wang JM, Zhang W, Wang W, Xu X: Recent advances in computational prediction of drug absorption and permeability in drug discovery. Curr Med Chem. 2006, 13: 2653-2667. 10.2174\/092986706778201558.","journal-title":"Curr Med Chem"},{"key":"367_CR27","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/1758-2946-4-31","volume":"4","author":"M Shen","year":"2012","unstructured":"Shen M, Tian S, Li Y, Li Q, Xu X, Wang J, Hou T: Drug-likeness analysis of traditional Chinese medicines: 1. property distributions of drug-like compounds, non-drug-like compounds and natural compounds from traditional Chinese medicines. J Cheminform. 2012, 4: 31-10.1186\/1758-2946-4-31.","journal-title":"J Cheminform"},{"key":"367_CR28","doi-asserted-by":"publisher","first-page":"2174","DOI":"10.1021\/ci2001428","volume":"51","author":"SR Langdon","year":"2011","unstructured":"Langdon SR, Brown N, Blagg J: Scaffold diversity of exemplified medicinal chemistry space. J Chem Inf Model. 2011, 51: 2174-2185. 10.1021\/ci2001428.","journal-title":"J Chem Inf Model"},{"key":"367_CR29","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/0006-2944(79)90061-9","volume":"21","author":"Y Sato","year":"1979","unstructured":"Sato Y, Hotta N, Sakamoto N, Matsuoka S, Ohishi N, Yagi K: Lipid peroxide level in plasma of diabetic-patients. Biochem Med. 1979, 21: 104-107. 10.1016\/0006-2944(79)90061-9.","journal-title":"Biochem Med"},{"key":"367_CR30","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1145\/102377.115768","volume":"11","author":"B Shneiderman","year":"1992","unstructured":"Shneiderman B: Tree Visualization with Tree-Maps - 2-D Space-Filling Approach. Acm Transactions on Graphics. 1992, 11: 92-99. 10.1145\/102377.115768.","journal-title":"Acm Transactions on Graphics"},{"key":"367_CR31","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1254\/jjp.37.365","volume":"37","author":"C Nishimura","year":"1985","unstructured":"Nishimura C, Kuriyama K: Alteration of lipid peroxide and endogenous antioxidant contents in retina of Streptozotocin-induced diabetic rats - effect of vitamin-a administration. Jpn J Pharmacol. 1985, 37: 365-372.","journal-title":"Jpn J Pharmacol"},{"key":"367_CR32","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1177\/1087057105281365","volume":"10","author":"D Rogers","year":"2005","unstructured":"Rogers D, Brown RD, Hahn M: Using extended-connectivity fingerprints with Laplacian-modified Bayesian analysis in high-throughput screening follow-up. J Biomol Screen. 2005, 10: 682-686. 10.1177\/1087057105281365.","journal-title":"J Biomol Screen"}],"container-title":["Journal of Cheminformatics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/1758-2946-5-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/1758-2946-5-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1758-2946-5-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T21:56:26Z","timestamp":1630533386000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcheminf.biomedcentral.com\/articles\/10.1186\/1758-2946-5-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,21]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,12]]}},"alternative-id":["367"],"URL":"https:\/\/doi.org\/10.1186\/1758-2946-5-5","relation":{},"ISSN":["1758-2946"],"issn-type":[{"value":"1758-2946","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,21]]},"assertion":[{"value":"3 October 2012","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 January 2013","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 January 2013","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"5"}}