RESUMO
The two isotopomers of teriflunomide were synthesized starting from isotopically stable-labeled stocks of [13 C]potassium cyanide and [1-13 C]ethyl bromoacetate. The two 13 C-labeled compounds 1a, b were applied in several NMR studies to study the E/Z ratio in different matrices. In a solution, such as dimethyl sulfoxide (DMSO), a dynamic equilibrium between E/Z-isomers (ratio of 8:92) was determined by initial 13 C-carbon NMR experiments. To get insights into the E/Z ratio of teriflunomide under in vivo conditions, advanced heteronuclear NMR (heteronuclear Overhauser effect spectroscopy [HOESY]) in D2 O and mixtures of D2 O/plasma were performed. Whereas NMR experiments in mixtures of water and plasma failed owing to extreme line broadening, NMR spectra in water at pH 7.4 showed only the Z-isomer.
Assuntos
Crotonatos/síntese química , Hidroxibutiratos/síntese química , Marcação por Isótopo/métodos , Nitrilas/síntese química , Toluidinas/síntese química , Acetatos/química , Isótopos de Carbono/química , Hidrocarbonetos Bromados/química , Isomerismo , Espectroscopia de Ressonância Magnética/métodos , Cianeto de Potássio/químicaRESUMO
DEAD-box proteins are an essential class of enzymes involved in all stages of RNA metabolism. The study of DEAD-box proteins is challenging in a native setting since they are structurally similar, often essential and display dosage sensitivity. Pharmacological inhibition would be an ideal tool to probe the function of these enzymes. In this work, we describe a chemical genetic strategy for the specific inactivation of individual DEAD-box proteins with small molecule inhibitors using covalent complementarity. We identify a residue of low conservation within the P-loop of the nucleotide-binding site of DEAD-box proteins and show that it can be mutated to cysteine without a substantial loss of enzyme function to generate electrophile-sensitive mutants. We then present a series of small molecules that rapidly and specifically bind and inhibit electrophile-sensitive DEAD-box proteins with high selectivity over the wild-type enzyme. Thus, this approach can be used to systematically generate small molecule-sensitive alleles of DEAD-box proteins, allowing for pharmacological inhibition and functional characterization of members of this enzyme family.
Assuntos
Monofosfato de Adenosina/análogos & derivados , Proteína DEAD-box 58/química , RNA Helicases DEAD-box/química , Proteína Oncogênica pp60(v-src)/química , Proteínas de Saccharomyces cerevisiae/química , Acrilamidas/síntese química , Acrilamidas/metabolismo , Acrilatos/síntese química , Acrilatos/metabolismo , Monofosfato de Adenosina/metabolismo , Motivos de Aminoácidos , Sequência de Aminoácidos , Substituição de Aminoácidos , Sítios de Ligação , Clonagem Molecular , Crotonatos/síntese química , Crotonatos/metabolismo , Cristalografia por Raios X , Proteína DEAD-box 58/antagonistas & inibidores , Proteína DEAD-box 58/genética , Proteína DEAD-box 58/metabolismo , RNA Helicases DEAD-box/antagonistas & inibidores , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Humanos , Cinética , Modelos Moleculares , Proteína Oncogênica pp60(v-src)/antagonistas & inibidores , Proteína Oncogênica pp60(v-src)/genética , Proteína Oncogênica pp60(v-src)/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Receptores Imunológicos , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMO
Investigations into the pharmacology of different types of cys-loop GABA receptor have relied for years on the chemical modification of GABA-like compounds. The GABA metabolite GABOB is an attractive molecule to modify due to its convenient chemical structure. In the process of developing new GABA-mimic compounds from GABOB as a starting compound three small molecule GABA derivatives were synthesized using a variety of chemical transformations. Amongst these, a new and reliable method to synthesize TACA (trans-4-aminocrotonic acid) is reported.
Assuntos
Crotonatos/farmacologia , Agonistas de Receptores de GABA-A/farmacologia , Receptores de GABA-A/metabolismo , Animais , Crotonatos/síntese química , Crotonatos/química , Relação Dose-Resposta a Droga , Agonistas de Receptores de GABA-A/síntese química , Agonistas de Receptores de GABA-A/química , Estrutura Molecular , Oócitos/efeitos dos fármacos , Relação Estrutura-Atividade , Xenopus laevisRESUMO
A novel series of meta-substituted ethanediamide and 2-butenediamide derivatives were synthesized and tested for their ability to inhibit electric eel acetylcholinesterase (AChE) and equine serum butyrylcholinesterase (BuChE). The synthesized compounds were evaluated against ChE enzymes using the colorimetric method described by Ellman et al. (Biochem. Pharmacol., 7, 1961). It was revealed that some synthesized compounds exhibited high anticholinesterase activity, among which compounds 1f and 2f were the most active inhibitors against BuChE (IC50 value=1.47 µM) and AChE (IC50 value=2.09 µM), respectively. Docking simulations revealed that the inhibitors 1f and 2f are capable of simultaneously binding the peripheral anionic site as well as the catalytic anionic site of both ChE enzymes. These derivatives are considered interesting candidates for Alzheimer's disease treatment.
Assuntos
Química Farmacêutica/métodos , Inibidores da Colinesterase/síntese química , Crotonatos/síntese química , Micro-Ondas , Oxalatos/síntese química , Sítios de Ligação , Inibidores da Colinesterase/metabolismo , Crotonatos/metabolismo , Oxalatos/metabolismoRESUMO
A flexible stereoselective approach to the common C1-C14 skeleton present in natural products of the pseudomonic acid family is described. The strategy has been extended and the total synthesis of pseudomonic acid methyl monate C was achieved. The key synthetic reactions utilized include Achmatowicz rearrangement, Johnson-Claisen rearrangement, Julia-Kocienski olefination, and Horner-Wadsworth-Emmons olefination reaction.
Assuntos
Química Orgânica/métodos , Crotonatos/síntese química , Mupirocina/análogos & derivados , Mupirocina/síntese química , Piranos/síntese química , Crotonatos/química , Indicadores e Reagentes , Mupirocina/química , Piranos/químicaRESUMO
Human dihydroorotate dehydrogenase (hDHODH), as the fourth and rate-limiting enzyme of the de novo pyrimidine synthesis pathway, is regarded as an attractive target for malignancy therapy. In the present study, a novel series of teriflunomide derivatives were designed, synthesized, and evaluated as hDHODH inhibitors. 13t was the optimal compound with promising enzymatic activity (IC50 = 16.0 nM), potent antiproliferative activity against human lymphoma Raji cells (IC50 = 7.7 nM), and excellent aqueous solubility (20.1 mg/mL). Mechanistically, 13t directly inhibited hDHODH and induced cell cycle S-phase arrest in Raji cells. The acute toxicity assay indicated a favorable safety profile of 13t. Notably, 13t displayed significant tumor growth inhibition activity with a tumor growth inhibition (TGI) rate of 81.4% at 30 mg/kg in a Raji xenograft model. Together, 13t is a promising inhibitor of hDHODH and a preclinical candidate for antitumor therapy, especially for lymphoma.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Crotonatos/química , Crotonatos/farmacologia , Di-Hidro-Orotato Desidrogenase/antagonistas & inibidores , Desenho de Fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Hidroxibutiratos/química , Hidroxibutiratos/farmacologia , Neoplasias/tratamento farmacológico , Nitrilas/química , Nitrilas/farmacologia , Toluidinas/química , Toluidinas/farmacologia , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Crotonatos/síntese química , Inibidores Enzimáticos/síntese química , Humanos , Hidroxibutiratos/síntese química , Neoplasias/patologia , Nitrilas/síntese química , Relação Estrutura-Atividade , Toluidinas/síntese químicaRESUMO
Catalpol has gained increasing attention for its potential contributions in controlling glycolipid metabolism and diabetic complications, which makes used as a very promising scaffold for seeking new anti-diabetic drug candidates. Acylation derivatives of catalpol crotonate (CCs) were designed as drug ligands of glutathione peroxidase (GSH-Px) based on molecular docking (MD) using Surfex-Docking method. Catalpol hexacrotonate (CC-6) was synthesized using microwave assisted method and characterized by FT-IR, NMR, HPLC and HRMS. The MD results indicate that with the increasing of esterification degree of hydroxyl, the C log P of CCs increased significantly, and the calculated total scores (Total_score) of CCs are all higher than that of catalpol. It shows that CCs maybe served as potential lead compounds for neuroprotective agents. It was found that the maximum Total_score of isomers in one group CCs is often not that the molecule with minimum energy. MD calculations show that there are five hydrogen bonds formed between CC-6 and the surrounding amino acid residues. Molecular dynamics simulation results show that the binding of CC-6 with GSH-Px is stable. CC-6 was screened for SH-SY5Y cells viability by MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay, the result indicates CC-6 can effectively reverse SZT induced cells apoptosis with dose-dependent manner, which can indirectly show that CC-6 is a potential neuroprotective agent.
Assuntos
Crotonatos/farmacologia , Glutationa Peroxidase/antagonistas & inibidores , Hipoglicemiantes/farmacologia , Glucosídeos Iridoides/farmacologia , Fármacos Neuroprotetores/farmacologia , Sítios de Ligação , Encefalopatias/tratamento farmacológico , Encefalopatias/enzimologia , Encefalopatias/etiologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Crotonatos/síntese química , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/enzimologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/enzimologia , Glutationa Peroxidase/química , Glutationa Peroxidase/metabolismo , Humanos , Ligação de Hidrogênio , Hipoglicemiantes/síntese química , Glucosídeos Iridoides/síntese química , Micro-Ondas , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/síntese química , Ligação ProteicaRESUMO
γ-Cyclodextrin-based metal-organic framework (γCD-MOF) crystals were successfully synthesized using a vapor diffusion method. An applicability of γCD-MOF for encapsulation of immunosuppressive disease-modifying antirheumatic drug leflunomide (LEF) was examined. Loading of LEF in γCD-MOF was performed by impregnation and co-crystallization. The empty and loaded γCD-MOFs were characterized using X-ray powder diffraction, N2 adsorption/desorption, thermogravimetric analysis, 1H NMR and FTIR spectroscopy. It was shown that in the presence of γCD-MOF leflunomide is transformed into its pharmacologically active form - teriflunomide that can be also applied alone in the treatment of multiple sclerosis. It was demonstrated that teriflunomide released from γCD-MOF has improved pharmacologically relevant properties such as solubility, dissolution rate and membrane permeability. It can be proposed that γCD-MOF can be considered as novel strategy for delivery of leflunomide.
Assuntos
Antirreumáticos/química , Crotonatos/síntese química , Leflunomida/química , Estruturas Metalorgânicas/química , Pró-Fármacos/química , Toluidinas/síntese química , gama-Ciclodextrinas/química , Liberação Controlada de Fármacos , Hidroxibutiratos , Cinética , Estruturas Metalorgânicas/síntese química , Nitrilas , Oxirredução , Permeabilidade , Porosidade , Solubilidade , gama-Ciclodextrinas/síntese químicaRESUMO
The enantioselective synthesis of the originally proposed structure of communiol C, an antibacterial 2,4-disubstituted tetrahydrofuran natural product from the coprophilous fungus Podospora communis, and its epimer via the Sharpless asymmetric dihydroxylation as the source of chirality led us to propose that the genuine stereochemistry of communiol C should be 3R, 5R, and 6S. The synthesis of the (3R,5R,6S)-isomer of communiol C and its good accordance with natural communiol C in every respect enabled us to confirm the newly proposed (3R,5R,6S)-stereochemistry for communiol C. The stereochemistries of structurally-related natural products (communiols A and B) of the same microbial origin were also revised through their total synthesis.
Assuntos
Acetatos/síntese química , Antibacterianos/síntese química , Butiratos/síntese química , Crotonatos/síntese química , Furanos/síntese química , Podospora/química , Acetatos/química , Produtos Biológicos , Butiratos/química , Crotonatos/química , Furanos/química , Estrutura Molecular , EstereoisomerismoRESUMO
A new highly active molecule, (2E, 2E)-4,4-trisulfanediylbis(but-2-enoic acid) (TSDB), was designed and synthesized through comparative molecular field analysis with the diallyl trisulfide structure of garlic. TSDB exerted a strong inhibitory effect against Staphylococcus aureus, with minimal inhibitory and minimal bactericidal concentrations of 16 and 128 µg/mL, respectively. TSDB destructed the integrity of the S. aureus cell membrane but weakly damaged the bacterial cell wall. TSDB also increased the conductivity and protein expression in microbial broth but minimally influenced the level of extracellular alkaline phosphatase. TSDB could be a novel food preservative.
Assuntos
Antibacterianos/farmacologia , Crotonatos/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/síntese química , Simulação por Computador , Crotonatos/síntese química , Staphylococcus aureus/crescimento & desenvolvimentoRESUMO
γ-Hydroxybutyric acid (GHB) is a neuroactive substance with specific high-affinity binding sites. To facilitate target identification and ligand optimization, we herein report a comprehensive structure-affinity relationship study for novel ligands targeting these binding sites. A molecular hybridization strategy was used based on the conformationally restricted 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) and the linear GHB analog trans-4-hydroxycrotonic acid (T-HCA). In general, all structural modifications performed on HOCPCA led to reduced affinity. In contrast, introduction of diaromatic substituents into the 4-position of T-HCA led to high-affinity analogs (medium nanomolar Ki) for the GHB high-affinity binding sites as the most high-affinity analogs reported to date. The SAR data formed the basis for a three-dimensional pharmacophore model for GHB ligands, which identified molecular features important for high-affinity binding, with high predictive validity. These findings will be valuable in the further processes of both target characterization and ligand identification for the high-affinity GHB binding sites.
Assuntos
Ácidos Carboxílicos/química , Crotonatos/química , Ciclopentanos/química , Hidroxibutiratos/química , Modelos Moleculares , Sítios de Ligação , Ácidos Carboxílicos/síntese química , Ácidos Carboxílicos/metabolismo , Crotonatos/síntese química , Crotonatos/metabolismo , Ciclopentanos/síntese química , Ciclopentanos/metabolismo , Desenho de Fármacos , Ligantes , Conformação Molecular , Relação Estrutura-AtividadeRESUMO
An efficient microwave-assisted protocol for the synthesis of 2-/3-methylthiochroman-4-ones by superacid-catalyzed alkylation followed by cyclic acylation (cyclization via intramolecular acylation) is described. Using easily accessible benzenethiols and crotonic acid/methacrylic acid with triflic acid (as catalyst of choice for needed optimal acidity), the reaction was tuned toward the formation of the cyclized products in good selectivity and yield. A mechanism involving the formation of carbenium-carboxonium superelectrophilic species is suggested.
Assuntos
Cromonas/síntese química , Crotonatos/síntese química , Metacrilatos/síntese química , Micro-Ondas , Fenóis/síntese química , Compostos de Sulfidrila/síntese química , Catálise , Cromonas/química , Crotonatos/química , Ciclização , Metacrilatos/química , Estrutura Molecular , Fenóis/química , Compostos de Sulfidrila/químicaRESUMO
The novel compound, (S)-amino-2-methyl-4-[(76)Br]bromo-3-(E)-butenoic acid (BrVAIB, [(76)Br]5), was characterized against the known system A tracer, IVAIB ([(123)I]8). [(76)Br]5 was prepared in a 51% ± 19% radiochemical yield with high radiochemical purity (≥98%). The biological properties of [(76)Br]5 were compared with those of [(123)I]8. Results showed that [(76)Br]5 undergoes mixed amino acid transport by system A and system L transport, while [(123)I]8 had less uptake by system L. [(76)Br]5 demonstrated higher uptake than [(123)I]8 in DBT tumors 1 h after injection (3.7 ± 0.4% ID/g vs 1.5 ± 0.3% ID/g) and also showed higher uptake vs [(123)I]8 in normal brain. Small animal PET studies with [(76)Br]5 demonstrated good tumor visualization of intracranial DBTs up to 24 h with clearance from normal tissues. These results indicate that [(76)Br]5 is a promising PET tracer for brain tumor imaging and lead compound for a mixed system A and system L transport substrate.
Assuntos
Neoplasias Encefálicas/diagnóstico , Encéfalo/patologia , Radioisótopos de Bromo/química , Crotonatos/química , Glioma/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Alanina/análogos & derivados , Alanina/farmacocinética , Aminação , Animais , Transporte Biológico , Encéfalo/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Radioisótopos de Bromo/farmacocinética , Crotonatos/síntese química , Crotonatos/farmacocinética , Glioma/metabolismo , Glioma/patologia , Radioisótopos do Iodo/farmacocinética , Masculino , Camundongos Endogâmicos BALB C , Compostos Radiofarmacêuticos/síntese química , Distribuição TecidualRESUMO
Twenty-three 4-substituted crotonic acid esters were tested for antifungal activity against Candida albicans, Aspergillus niger, Mucor mucedo, and Trichophyton mentagrophytes. For the analogues of the methyl ester containing substituents in the 4 position, the following order of fungitoxicity was observed: I greater than Br greater than Cl greater than CH3S greater than CH3O greater than F=H. Of the homologues of the esters of the 4-iodo and 4-bromo compounds which included methyl, ethyl, n-propyl, n-butyl, n-pentyl, and n-hexyl, ethyl 4-iodocrotonate was most toxic to the four fungi at pH 7.0 in the presence of 10% beef serum (C. albicans, 18mug/ml, A. niger, 40 mug/ml, M. mucedo, 5 mug/ml, T. mentagrophytes, 4 mug/ml). It is believed that the mechanism of fungitoxicity is due, in part, to a nucleophilic reaction involving SH-containing compounds. This is based on the correlation of fungitoxicity with the order of leaving groups in the nucleophilic reaction and the protection against the toxicity of the test compounds to the fungi by cysteine and glutathione.
Assuntos
Antifúngicos/síntese química , Butiratos/síntese química , Crotonatos/síntese química , Aspergillus niger/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Crotonatos/farmacologia , Testes de Sensibilidade Microbiana , Mucor/efeitos dos fármacos , Trichophyton/efeitos dos fármacosRESUMO
The antitumor activity of 2-crotonyloxymethyl-2-cyclohexenone (COMC-6) is not the result of the GSH conjugate (GSMC-6) formed inside tumor cells, as the diethyl ester prodrug form of GSMC-6 displays little antitumor activity with B16 melanotic melanoma in vitro (IC(50) > 460 microM) versus COMC-6 (IC(50) 0.041 microM) and its five- and seven-membered ring homologues. Antitumor activity probably results from a reactive intermediate that forms during conjugation of the COMCs with intracellular GSH.
Assuntos
Antineoplásicos/farmacologia , Crotonatos/farmacologia , Cicloexanonas/farmacologia , Cicloparafinas/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Divisão Celular/efeitos dos fármacos , Crotonatos/síntese química , Crotonatos/química , Cicloexanos/síntese química , Cicloexanos/química , Cicloexanos/farmacologia , Cicloexanonas/síntese química , Cicloexanonas/química , Cicloparafinas/síntese química , Cicloparafinas/química , Glutationa/química , Glutationa/metabolismo , Camundongos , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Multiple sclerosis (MS) often results in chronic inflammatory and autoimmune disorders, and recent developments in understanding the disease pathogenesis has lead to newer therapeutic options for the treatment of the disease. The development of small molecule drugs with improved efficacy, better tolerability, and oral administration has received a new impetus with the discovery of newer classes of drugs. In this review, we have summarized the hitherto known synthetic strategies of fingolimod, laquinimod, cladribine, and teriflunomide reported in the literature which are the key small molecules and the first oral drug candidates for MS in various stages of clinical development or have been launched in the market.
Assuntos
Cladribina/uso terapêutico , Crotonatos/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Propilenoglicóis/uso terapêutico , Quinolonas/uso terapêutico , Bibliotecas de Moléculas Pequenas/uso terapêutico , Esfingosina/análogos & derivados , Toluidinas/uso terapêutico , Cladribina/síntese química , Cladribina/química , Crotonatos/síntese química , Crotonatos/química , Cloridrato de Fingolimode , Humanos , Hidroxibutiratos , Estrutura Molecular , Nitrilas , Propilenoglicóis/síntese química , Propilenoglicóis/química , Quinolonas/síntese química , Quinolonas/química , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Esfingosina/síntese química , Esfingosina/química , Esfingosina/uso terapêutico , Toluidinas/síntese química , Toluidinas/químicaRESUMO
An effective ligand-free Suzuki coupling protocol to unite methyl (E)-4-bromobut-2-enoate with several arylboronic acids has been accomplished. Thus, a number of variously functionalized methyl 4-arylcrotonates have been achieved in high to excellent yields under mild conditions. This method enables the preparation of diverse aryl-substituted cores of HIV-1 protease inhibitors.
Assuntos
Ácidos Borônicos/química , Crotonatos/síntese química , Inibidores da Protease de HIV/síntese química , Catálise , Técnicas de Química Combinatória , Crotonatos/química , Crotonatos/farmacologia , Inibidores da Protease de HIV/química , Inibidores da Protease de HIV/farmacologia , Humanos , Estrutura Molecular , Paládio/químicaRESUMO
The first asymmetric sulfa-Michael addition of thiols to 4,4,4-trifluorocrotonates for the construction of a stereogenic center bearing a unique trifluoromethyl group and a sulfur atom has been achieved in high yields and excellent enantioselectivities with a 1 mol % bifunctional organocatalyst. Subsequent transformation led to the expedient preparation of enantioenriched thiochroman-4-one and the key intermediate of the potent inhibitor of MMP-3, (R)-γ-trifluoromethyl γ-sulfone hydroxamate.
Assuntos
Crotonatos/síntese química , Flúor/química , Compostos de Sulfidrila/química , Enxofre/química , Catálise , Inibidores Enzimáticos/química , Inibidores de Metaloproteinases de Matriz , Estrutura Molecular , EstereoisomerismoRESUMO
Antiproliferative activity of 27 phenyl-substituted 4-aryl-4-oxo-2-butenoic acids (aroylacrylic acids) toward Human cervix carcinoma (HeLa), Human chronic myelogenous leukemia (K562) and Human colon tumor (LS174) cell lines in vitro are reported. Compounds are active toward all examined cell lines. The most active compounds bear two or three branched alkyl or cycloalkyl substituents on phenyl moiety having potencies in low micromolar ranges. One of most potent derivatives arrests the cell cycle at S phase in HeLa cells. The 3D QSAR study, using molecular interaction fields (MIF) and derived alignment independent descriptors (GRIND-2), rationalize the structural characteristics correlated with potency of compounds. Covalent chemistry, most possibly involved in the mode of action of reported compounds, was quantitatively accounted using frontier molecular orbitals. Pharmacophoric pattern of most potent compounds are used as a template for virtual screening, to find similar ones in database of compounds screened against DTP-NCI 60 tumor cell lines. Potency of obtained hits is well predicted.