A topological substructural approach applied to the computational prediction of rodent carcinogenicity.


:The carcinogenic activity has been investigated by using a topological substructural molecular design approach (TOPS-MODE). A discriminant model was developed to predict the carcinogenic and noncarcinogenic activity on a data set of 189 compounds. The percentage of correct classification was 76.32%. The predictive power of the model was validated by three test: an external test set (compounds not used in the develop of the model, with a 72.97% of good classification), a leave-group-out cross-validation procedure (4-fold full cross-validation, removing 20% of compounds in each cycle, with a good prediction of 76.31%) and two external prediction sets (the first and second exercises of the National Toxicology Program). This methodology evidenced that the hydrophobicity increase the carcinogenic activity and the dipole moment of the molecule decrease it; suggesting the capacity of the TOPS-MODE descriptors to estimate this property for new drug candidates. Finally, the positive and negative fragment contributions to the carcinogenic activity were identified (structural alerts) and their potentialities in the lead generation process and in the design of 'safer' chemicals were evaluated.


Bioorg Med Chem


Helguera AM,Cabrera Pérez MA,González MP,Ruiz RM,González Díaz H




Has Abstract


2005-04-01 00:00:00














  • NO-glibenclamide derivatives: prototypes of a new class of nitric oxide-releasing anti-diabetic drugs.

    abstract::Endothelial dysfunction and consequent reduction of biosynthesis of endogenous nitric oxide (NO) play an important pathogenetic role in the cardiovascular complications associated with type II diabetes. In this work, the hybrid drugs 3a and 3b, nitrooxymethylbenzoate-derivatives of 1 (which is a hydroxylated active me...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Calderone V,Rapposelli S,Martelli A,Digiacomo M,Testai L,Torri S,Marchetti P,Breschi MC,Balsamo A

    更新日期:2009-08-01 00:00:00

  • Design and synthesis of an all-in-one 3-(1,1-difluoroprop-2-ynyl)-3H-diazirin-3-yl functional group for photo-affinity labeling.

    abstract::A novel radioisotope-free photo-affinity probe containing the 3-(1,1-difluoroprop-2-ynyl)-3H-diazirin-3-yl functional group was designed and synthesized. This very compact functionality is envisaged to allow photochemically-induced coupling of a compound to its target followed by click reaction coupling with an azido-...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kumar NS,Young RN

    更新日期:2009-08-01 00:00:00

  • Synthesis of dihydronaphthofurandiones and dihydrofuroquinolinediones with trypanocidal activity and analysis of their stereoelectronic properties.

    abstract::The synthesis of dihydronaphthofurandione and dihydrofuroquinolinedione derivatives 4-11 was performed through Diels-Alder reactions of dihydrobenzofurandione 1 with several carbodienes and acrolein N,N-dimethylhydrazone. Then, the use of 5-bromobenzofurandione 2 toward 1,3-pentadiene and the 1-azadiene afforded quino...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Tapia RA,Salas C,Morello A,Maya JD,Toro-Labbé A

    更新日期:2004-05-01 00:00:00

  • Identification of 2-[2-(4-tert-butylphenyl)ethyl]-N-(4-fluorophenyl)-1,2,3,4-tetrahydroisoquinoline-6-sulfonamide (29) as an orally available MGAT2 inhibitor.

    abstract::MGAT2 (monoacylglycerol acyltransferase 2) is expected to be an attractive target for the drug treatment of obesity, diabetes, and other disease. We describe our exploration and structure-activity relationship (SAR) study of 2,3-dihydro-1H-isoindole-5-sulfonamide derivatives. In this study, we identified 29 as an oral...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Busujima T,Tanaka H,Shirasaki Y,Munetomo E,Saito M,Kitano K,Minagawa T,Yoshida K,Osaki N,Sato N

    更新日期:2015-09-01 00:00:00

  • Synthesis and structure activity relationships of novel non-peptidic metallo-aminopeptidase inhibitors.

    abstract::Racemic derivatives of 3-amino-2-tetralone were synthesised and evaluated for their ability to inhibit metallo-aminopeptidase activities. New compounds substituted in position 2 by methyl ketone, substituted oximes or hydroxamic acids as well as heterocyclic derivatives were evaluated against representative members of...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Albrecht S,Defoin A,Salomon E,Tarnus C,Wetterholm A,Haeggström JZ

    更新日期:2006-11-01 00:00:00

  • Development and evaluation of a 68Ga labeled pamoic acid derivative for in vivo visualization of necrosis using positron emission tomography.

    abstract::In this study, we labeled N,N'-bis(diethylenetriamine pentaacetic acid)-pamoic acid bis-hydrazide (bis-DTPA-PA) with the generator produced PET radionuclide gallium-68 and evaluated 68Ga-bis-DTPA-PA as a potential tracer for in vivo visualization of necrosis by positron emission tomography (PET). Radiolabeling was ach...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Prinsen K,Li J,Vanbilloen H,Vermaelen P,Devos E,Mortelmans L,Bormans G,Ni Y,Verbruggen A

    更新日期:2010-07-15 00:00:00

  • Fluorine-18 (18F)-labeled retinoid x receptor (RXR) partial agonist whose tissue transferability is affected by other RXR ligands.

    abstract::Bexarotene (1), a retinoid X receptor (RXR) agonist approved for the treatment of cutaneous T cell lymphoma (CTCL), was reported to migrate into baboon brain based on findings obtained by positron emission tomography (PET) with a 11C-labeled tracer. However, co-administration of non-radioactive 1 had no effect on the ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Takamura Y,Shibahara O,Watanabe M,Fujihara M,Yamada S,Akehi M,Sasaki T,Hirano H,Kakuta H

    更新日期:2019-07-15 00:00:00

  • 11-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine derivatives as novel topoisomerase I-targeting agents.

    abstract::Several 11-substituted benzo[i]phenanthridine derivatives were synthesized, and their TOP1-targeting activity and cytotoxicity were assessed. Comparative data indicate that TOP1-targeting was often the primary molecular target associated with their cytotoxicity. Several 11-aminoalkyl derivatives, 11-aminocarboxy deriv...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Feng W,Satyanarayana M,Tsai YC,Liu AA,Liu LF,LaVoie EJ

    更新日期:2008-09-15 00:00:00

  • Identification of bis-quindolines as new antiinfective agents.

    abstract::Several N-substituted quindolines were made to further evaluate the role of N-alkylation on the activity of indoloquinolines as antifungal agents. While N-5 substitution is required for these activities, N-10 alkylation alone leads to inactive products but is tolerated in the presence of N-5 alkyl groups. It was also ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Mardenborough LG,Zhu XY,Fan P,Jacob MR,Khan SI,Walker LA,Ablordeppey SY

    更新日期:2005-06-02 00:00:00

  • Asymmetric reduction of 3-aryl-3-keto esters using Rhizopus species.

    abstract::Ethyl 3-aryl-3-oxopropanoates (aryl: phenyl, 2-fluorophenyl, 3-nitrophenyl, and 4-nitrophenyl) were reduced enantioselectively to the corresponding (S)-alcohols by the fungus Rhizopus arrhizus and other Rhizopus sp. The best results were generally obtained with Rhizopus arrhizus (wild type) and Rhizopus nivius NCIM 95...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Salvi NA,Chattopadhyay S

    更新日期:2006-07-15 00:00:00

  • Docking and hydropathic scoring of polysubstituted pyrrole compounds with antitubulin activity.

    abstract::Compounds that bind at the colchicine site of tubulin have drawn considerable attention with studies indicating that these agents suppress microtubule dynamics and inhibit tubulin polymerization. Data for 18 polysubstituted pyrrole compounds are reported, including antiproliferative activity against human MDA-MB-435 c...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Tripathi A,Fornabaio M,Kellogg GE,Gupton JT,Gewirtz DA,Yeudall WA,Vega NE,Mooberry SL

    更新日期:2008-03-01 00:00:00

  • Palladium(II) saccharinate complexes with bis(2-pyridylmethyl)amine induce cell death by apoptosis in human breast cancer cells in vitro.

    abstract::The outcomes of breast cancer patients are still poor although new compounds have recently been introduced into the clinic. Therefore, novel chemical approaches are required. In the present study, palladium(II) and corresponding platinum(II) complexes containing bis(2-pyridylmethyl)amine (bpma) and saccharine were syn...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ari F,Ulukaya E,Sarimahmut M,Yilmaz VT

    更新日期:2013-06-01 00:00:00

  • Synthesis of 26-hydroxy-22-oxocholestanic frameworks from diosgenin and hecogenin and their in vitro antiproliferative and apoptotic activity on human cervical cancer CaSki cells.

    abstract::Certain steroidal compounds have demonstrated an antiproliferative effect against several tumor cell lines; however, their complete role on cancer cells is not currently established. Herein, we report the synthesis and evaluation of two new 26-hydroxy-22-oxocholestanic steroids on cervical cancer CaSki cells. The titl...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Fernández-Herrera MA,López-Muñoz H,Hernández-Vázquez JM,López-Dávila M,Escobar-Sánchez ML,Sánchez-Sánchez L,Pinto BM,Sandoval-Ramírez J

    更新日期:2010-04-01 00:00:00

  • Design, synthesis and evaluation of flavonoid derivatives as potent AChE inhibitors.

    abstract::A new series of flavonoid derivatives have been designed, synthesized and evaluated as potent AChE inhibitors. Most of them showed more potent inhibitory activities to AChE than rivastigmine. The most potent inhibitor isoflavone derivative 10d inhibit AChE with a IC(50) of 4 nM and showed high BChE/AChE inhibition rat...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sheng R,Lin X,Zhang J,Chol KS,Huang W,Yang B,He Q,Hu Y

    更新日期:2009-09-15 00:00:00

  • Visual observation of G-quadruplex DNA with the label-free fluorescent probe silole with aggregation-induced emission.

    abstract::AIE molecule silole 1 could be used to detect G-quadruplex formation using an exonuclease I hydrolysis assay. This visual observation of G-quadruplexes has been successfully used in investigating multiple G-quadruplexes, including the one-stranded telomeric, c-myc, c-kit, VEGF G-quadruplexes, and a d(G(4)T(4)G(4)) int...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Huang J,Wang M,Zhou Y,Weng X,Shuai L,Zhou X,Zhang D

    更新日期:2009-11-15 00:00:00

  • Synthesis and preliminary biological evaluation of radiolabeled 5-BDBD analogs as new candidate PET radioligands for P2X4 receptor.

    abstract::P2X4 receptor has become an interesting molecular target for treatment and PET imaging of neuroinflammation and associated brain diseases such as Alzheimer's disease. This study reports the first design, synthesis, radiolabeling and biological evaluation of new candidate PET P2X4 receptor radioligands using 5-BDBD, a ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wang M,Gao M,Meyer JA,Peters JS,Zarrinmayeh H,Territo PR,Hutchins GD,Zheng QH

    更新日期:2017-07-15 00:00:00

  • Bis-pyrene-labeled molecular beacon: a monomer-excimer switching probe for the detection of DNA base alteration.

    abstract::A new bis-pyrene-labeled oligonucleotide probe (BP-probe) has been designed for the detection of a single base mismatch in single strand (ss) DNA as a target. The sequence of BP-probe was chosen to form stem-loop structure similar to a molecular beacon (MB-probe), yielding bis-pyrene-labeled molecular beacon (BP-MB-pr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yamana K,Ohshita Y,Fukunaga Y,Nakamura M,Maruyama A

    更新日期:2008-01-01 00:00:00

  • Synthesis and biological evaluation of purine derivatives incorporating metal chelating ligands as HIV integrase inhibitors.

    abstract::Because of its essential role in HIV replication and lack of human counterpart, HIV integrase is an attractive target for the development of novel anti-AIDS agents. Among the recently developed integrase inhibitors, only the alpha,gamma-diketo acid (DKA) compounds were biologically validated as potent and selective in...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Li X,Vince R

    更新日期:2006-08-15 00:00:00

  • Synthesis and structure-activity relationship studies on tryprostatin A, an inhibitor of breast cancer resistance protein.

    abstract::Tryprostatin A is an inhibitor of breast cancer resistance protein, consequently a series of structure-activity studies on the cell cycle inhibitory effects of tryprostatin A analogues as potential antitumor antimitotic agents have been carried out. These analogues were assayed for their growth inhibition properties a...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Jain HD,Zhang C,Zhou S,Zhou H,Ma J,Liu X,Liao X,Deveau AM,Dieckhaus CM,Johnson MA,Smith KS,Macdonald TL,Kakeya H,Osada H,Cook JM

    更新日期:2008-04-15 00:00:00

  • Natural products in crop protection.

    abstract::The tremendous increase in crop yields associated with the 'green' revolution has been possible in part by the discovery and utilization of chemicals for pest control. However, concerns over the potential impact of pesticides on human health and the environment has led to the introduction of new pesticide registration...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Dayan FE,Cantrell CL,Duke SO

    更新日期:2009-06-15 00:00:00

  • Synthesis and biological evaluation of new camptothecin derivatives obtained by modification of position 20.

    abstract::The preparation and biological evaluation of a novel series of dimeric camptothecin derivatives are described. All the new compounds showed a significant ability to inhibit human tumor cell growth with IC(50) values ranging from 0.03 to 12.2 μM. The interference with the activity of the nuclear enzymes topoisomerases ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Riva E,Comi D,Borrelli S,Colombo F,Danieli B,Borlak J,Evensen L,Lorens JB,Fontana G,Gia OM,Via LD,Passarella D

    更新日期:2010-12-15 00:00:00

  • Toward the discovery of dual HCMV-VZV inhibitors: Synthesis, structure activity relationship analysis, and cytotoxicity studies of long chained 2-uracil-3-yl-N-(4-phenoxyphenyl)acetamides.

    abstract::The need for novel therapeutic options to fight herpesvirus infections still persists. Herein we report the design, synthesis and antiviral evaluation of a new family of non-nucleoside antivirals, derived from 1-[ω-(4-bromophenoxy)alkyl]uracil derivatives--previously reported inhibitors of human cytomegalovirus (HCMV)...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Babkov DA,Khandazhinskaya AL,Chizhov AO,Andrei G,Snoeck R,Seley-Radtke KL,Novikov MS

    更新日期:2015-11-01 00:00:00

  • Anti-HBV and cytotoxic activities of pyranocoumarin derivatives.

    abstract::Four natural pyranocoumarins clausenidin (1), nordentatin (2), clausarin (3), and xanthoxyletin (4) were isolated from the medicinal plant Clausena excavata. Recently, we found that 1 and 2 suppressed hepatitis B virus surface antigen in HepA2 cells, and in addition, 1-3 showed cytotoxic activity against four human ca...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Su CR,Yeh SF,Liu CM,Damu AG,Kuo TH,Chiang PC,Bastow KF,Lee KH,Wu TS

    更新日期:2009-08-15 00:00:00

  • Development of a novel class of peroxisome proliferator-activated receptor (PPAR) gamma ligands as an anticancer agent with a unique binding mode based on a non-thiazolidinedione scaffold.

    abstract::We previously identified dibenzooxepine derivative 1 as a potent PPARγ ligand with a unique binding mode owing to its non-thiazolidinedione scaffold. However, while 1 showed remarkably potent MKN-45 gastric cancer cell aggregation activity, an indicator of cancer differentiation-inducing activity induced by PPARγ acti...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yamamoto K,Tamura T,Nakamura R,Hosoe S,Matsubara M,Nagata K,Kodaira H,Uemori T,Takahashi Y,Suzuki M,Saito JI,Ueno K,Shuto S

    更新日期:2019-11-15 00:00:00

  • Pyrrolomycins as antimicrobial agents. Microwave-assisted organic synthesis and insights into their antimicrobial mechanism of action.

    abstract::New compounds able to counteract staphylococcal biofilm formation are needed. In this study we investigate the mechanism of action of pyrrolomycins, whose potential as antimicrobial agents has been demonstrated. We performed a new efficient and easy method to use microwave organic synthesis suitable for obtaining pyrr...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Raimondi MV,Listro R,Cusimano MG,La Franca M,Faddetta T,Gallo G,Schillaci D,Collina S,Leonchiks A,Barone G

    更新日期:2019-03-01 00:00:00

  • Design, synthesis, radiolabeling and in vivo evaluation of potential positron emission tomography (PET) radioligands for brain imaging of the 5-HT₇ receptor.

    abstract::Here we describe the design, synthesis, and pharmacological evaluation of a set of compounds structurally related to the high affinity serotonin 5-HT7 receptor agonist N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (6, LP-211). Specific structural modifications were performed in order to maintain affini...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Lacivita E,Niso M,Hansen HD,Di Pilato P,Herth MM,Lehel S,Ettrup A,Montenegro L,Perrone R,Berardi F,Colabufo NA,Leopoldo M,Knudsen GM

    更新日期:2014-03-01 00:00:00

  • Novel FXR (farnesoid X receptor) modulators: Potential therapies for cholesterol gallstone disease.

    abstract::Metabolic disorders such as diabetes are known risk factors for developing cholesterol gallstone disease (CGD). Cholesterol gallstone disease is one of the most prevalent digestive diseases, leading to considerable financial and social burden worldwide. Ursodeoxycholic acid (UDCA) is the only bile acid drug approved b...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Yu DD,Andrali SS,Li H,Lin M,Huang W,Forman BM

    更新日期:2016-09-15 00:00:00

  • The influence of halogen substituents on the biological properties of sulfur-containing flavonoids.

    abstract::A series of halogen-substituted tricyclic flavonoids containing a 1,3-dithiol-2-ylium moiety has been synthesized from the corresponding 3-dithiocarbamic flavanones. The influence of halogen substituents on the antibacterial properties of the tricyclic flavonoids has been investigated against Staphylococcus aureus and...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Bahrin LG,Sarbu LG,Hopf H,Jones PG,Babii C,Stefan M,Birsa ML

    更新日期:2016-07-15 00:00:00

  • Glycosyl bis-porphyrin conjugates: synthesis and potential application in PDT.

    abstract::Syntheses of new glycosylated neutral and cationic porphyrin dimers linked at the meso-position via a flexible hydrocarbon chain are described. A detailed 1H and 13C NMR study allows their complete structural elucidation. The UV-visible, fluorescence and MALDI mass spectra are also presented. Photocytotoxicities of th...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sol V,Chaleix V,Champavier Y,Granet R,Huang YM,Krausz P

    更新日期:2006-12-01 00:00:00

  • Molecular design of N-linked tetravalent glycosides bearing N-acetylglucosamine, N,N'-diacetylchitobiose and N-acetyllactosamine: Analysis of cross-linking activities with WGA and ECA lectins.

    abstract::Two types of nonspacer- and spacer-N-linked tetravalent glycosides bearing N-acetylglucosamine (GlcNAc), N,N'-diacetylchitobiose [(GlcNAc)(2)] and N-acetyllactosamine (LacNAc) were designed and prepared as glycomimetics. The interactions of wheat germ (Triticum vulgaris) agglutinin (WGA) and coral tree (Erythrina cris...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Masaka R,Ogata M,Misawa Y,Yano M,Hashimoto C,Murata T,Kawagishi H,Usui T

    更新日期:2010-01-15 00:00:00