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Frequency and Importance of Six Functional Groups That Play a Role in Drug Discovery

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Frequency and Importance of Six Functional Groups That Play a Role in Drug Discovery BIOSCIENCES BIOTECHNOLOGY RESEARCH ASIA, September 2018. Vol. 15(3), p. 541-548 Frequency and Importance of Six Functional Groups that Play a Role in Drug Discovery Sholeh Maslehat, Soroush Sardari* and Mahboube Ganji Arjenaki 1Drug Design and Bioinformatics Unit, Department of Medical Biotechnology, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran http://dx.doi.org/10.13005/bbra/2659 (Received: 05 July 2018; accepted: 18 September 2018) Small molecules are composed of chemical functional groups; they are sets of connected atoms or atom groups that determine properties and reactivity of the parent molecule. DrugBank is a rich source of information that containing molecular data about small molecules, their mechanisms, pharmaceutical interaction and targets. In this study, After collecting data of small drug molecules from DrugBank database and classifying them in different categories based on their mechanism of action, the therapeutic properties of the molecules were recorded. Finally, the functional group from the pharmaceutical structures were elucidated and registered for each group. The functional groups were divided into five distinct groups in drug design, and a correlation between identified functional group to pharmaceutical structure were indicated according to the classified functional groups of small molecule and drug categories; then defined their frequency in categories, at high abundant functional group present in categories reported. The most frequent rings were benzene and cyclohexane; the common acid functionality had been acetate (carboxy-); three most repeated saturated heterocyles are piperidine, piperazine and azetidine; among the unsaturated heterocyles, pyridine, imidazole and indole are noticed; This database, that may be guidance for researchers with the aim at designing new drugs. Keywords: Small molecules, functional groups. The navigate of functional groups (FGs) for small molecules could also be obtained by are sets of connected atoms or atom groups that identifying the molecules chemical functional determine properties and reactivity of parent groups using objective and computable criteria5. molecule, forms basis of organic chemistry, The common characteristic of the chemical analytical chemistry, medicinal chemistry and structures of the global small molecular drugs could also chemical nomenclature. Therefore, It defines be used as a criterion to guide the selection, design the characteristic physical, chemical properties and optimization of drug purpose compounds of families of organic compounds and indicates and candidates in the early stages of preclinical the classification of their1-3. Functional groups research, therefore it would be increase the success have relatively constant characteristics even when rate of drug development and eliminate those poor connected to different structures4. Small molecules drug-like compounds in advance and avoid more can be composed of independent chemical research and development expenses. Therefore, the functional groups, therefore a classification study of the key chemical structure characteristics *Corresponding author E-mail: [email protected] This is an Open Access article licensed under a Creative Commons license: Attribution 4.0 International (CC-BY). Published by Oriental Scientific Publishing Company © 2018 542 MASLEHAT et al., Biosci., Biotech. Res. Asia, Vol. 15(3), 541-548 (2018) of small molecule drugs has significant theoretical computer. The SMILES is a useful specification, and practical value6. Researchers who are interested real chemical language with simple vocabulary in chemical compounds for drug design, small (atoms and bonds) and only a few grammar molecule drugs especially face several problems. rules. representations of structure of SMILES They might want to find the common features of can be used in turn as “words” in the vocabulary a category of drugs for design a new drug with of other languages that designed for storage of similar targeting, or how a group of small molecule chemical information and chemical intelligence. is converted into other types of compounds, even Also the representations of SMILES are generally when the total structures are not specified and considered for the advantage of being more how a small molecule is fined or designed, when human-readable than other line notation systems. biological molecular target is defined. Moreover, it has a wide base of software support DrugBank (>6000 approved and with extensive theoretical backing. experimental drugs) (http://www.drugbank.ca) is a Functional groups (FGs) are specific web-enabled database and a comprehensive online moieties of atoms, or groups of atoms in the database containing molecular information about structure of molecules that have consistent drugs, their mechanisms, interactions and targets. properties and are responsible for characteristic Number of investigational drugs, small molecule chemical and biological activity of compounds. drugs, drug-drug interactions, SNP-associated It defines the characteristic physical and chemical drug effects has grown in the database in more properties of families of organic compounds. The than 10 years. DrugBank 3.0 has been contained same functional groups often have the same or data on drug metabolism, absorption, distribution, similar chemical or biological features and will metabolism, excretion and toxicity (ADMET) undergo the same or similar chemical reactions and other kinds of quantitative structure activity whenever it occurs in different compounds, relationships (QSAR) information also numbers however the presence of other functional groups of small molecule drugs in GrugBank 3.0 more and the size of the molecules can be effective on than previous versions (4, 7-10). Therefore, its their properties11. database is a good data resource for small molecule drugs, that may be guidance for researchers with RESULTS aim design new drugs. Based on our knowledge, no evidence or software defined that, how are In this article, we studied 114 functional frequency drug functional groups between small groups that were more important in drug design. molecules and relative drug categories available In the next step, the functional group extracts from at DrugBank 3.0. In this study, we classified the pharmaceutical structures. functional groups of small molecule drugs base The Functional groups use in this study on drug categories, then defined their frequency We divided Functional groups based on in categories, at result high abundant functional the structural similarities of their molecules to group into categories reported. five familiar groups: Saturated cyclic, Unsaturated cyclic, Heterocyclic compound unsaturated, Acids, MATERIAL AND METHOD Amide, Aldehydes (the carbonyl group is polar), Neutral aromatic ( Polar Deactivated). Then we Simplified Molecular Input Line Entry sketched their graphs System (SMILES) is a simple chemical line Group 1: Functional groups that have notation (a typographical method using printable saturated cyclic properties include fragmentation: characters) for representing molecules and Cyclohexane ,cyclopropane, cyclobutane, reactions that was introduced by David Weininger cycloheptane, cyclopentane, cyclooctane, that are in 198711 originally. SMILES string is a linear text distinguished by the yellow color in (Fig 1). format to represent the two- or three-dimensional of Group 2: Functional Groups that have molecular structures as a zero-dimensional string, unsaturated cyclic properties include fragmentation: which can described the connectivity, isomeric and benzene, naphthalene that are distinguished orange chirality of molecules so that it can be used by the in (Fig 1). MASLEHAT et al., Biosci., Biotech. Res. Asia, Vol. 15(3), 541-548 (2018) 543 Group 3: Functional groups that are fragmentation PYRIDINE , Thiophene, THIAZOLE Heterocyclic compound unsaturated , which , isoxazole, oxazole, pyrazole , Indol, imidazole, include fragmentation aziridine, dioxirane, furan, pyrrole, acridine, purin, pyrimidine, oxirane, thiirane, azetidine, oxetane, thietane. pentadeca, benzodiazepin, imidazolidino , Pyrrolidine, oxolane, thiolane, piperidine, oxazolidin, Tetrazole, triazol , triazol, Pteridin-4-ol, piperazin, 1,4-dioxane, 1,4-dithiane, morpholine, pyrazine, Benzopyran=(chromene), benzodiazol, thiomorpholine, Tropane, azapentacyclo, oxane, Benzothiazole, 1,4-Dihydroquinoline, Which are 1,3-diazinane, azabicyclo, Imidazolidine, distinguished by purple in (Fig 1). Imidazolidine, phenothiazin that are distinguished Group 5: Functional groups that are by red in (Fig 1). Acids, which include fragmentation carboxylate Group 4: : Functional groups that are Anion, sulfinic acid, sulfonic acid, Vendors, Heterocyclic compound saturated , which include phosphodiester, phosphonic acid, phosphate, Group 1. Total number of saturated cyclic moieties in various therapeutic categories mentioned in DrugBank Group 2. Saturated cyclic rings Group 3. Heterocyclic saturated moieties 544 MASLEHAT et al., Biosci., Biotech. Res. Asia, Vol. 15(3), 541-548 (2018) acetate, Which are distinguished in dark red in (Fig Group 7 : Functional Groups that have 1). Aldehydes the carbonyl group is polar properties Group 6: : Functional groups that are include fragmentation ether, HYDROPEROXIDE, Amides, which include fragmentation Amine NH3, peroxide, peroxide, Alcohol, Tertiary Amine, THIOUREA, Amine NH2 , Thioamide Which are imine, azide, azo compound, Nitrate, Nitrite, distinguished in green
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