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1.
Chemistry ; 25(4): 1064-1075, 2019 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-30357947

RESUMO

During an investigation into the potential union of Lewis basic isothiourea organocatalysis and gold catalysis, the formation of gold-isothiourea complexes was observed. These novel gold complexes were formed in high yield and were found to be air- and moisture stable. A series of neutral and cationic chiral gold(I) and gold(III) complexes bearing enantiopure isothiourea ligands was therefore synthesized and fully characterized. The steric and electronic properties of the isothiourea ligands was assessed through calculation of their percent buried volume and the synthesis and analysis of novel iridium(I)-isothiourea carbonyl complexes. The novel gold(I)- and gold(III)-isothiourea complexes have been applied in preliminary catalytic and biological studies, and display promising preliminary levels of catalytic activity and potency towards cancerous cell lines and clinically relevant enzymes.

2.
Chem Cent J ; 12(1): 29, 2018 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-29541952

RESUMO

BACKGROUND: Design and synthesis of pyrazole-dimedone derivatives were described by one-pot multicomponent reaction as new antimicrobial agents. These new molecular framework were synthesized in high yields with a broad substrate scope under benign conditions mediated by diethylamine (NHEt2). The molecular structures of the synthesized compounds were assigned based on different spectroscopic techniques (1H-NMR, 13C-NMR, IR, MS, and CHN). RESULTS: The synthesized compounds were evaluated for their antibacterial and antifungal activities against S. aureus ATCC 29213, E. faecalis ATCC29212, B. subtilis ATCC 10400, and C. albicans ATCC 2091 using agar Cup plate method. Compound 4b exhibited the best activity against B. subtilis and E. faecalis with MIC = 16 µg/L. Compounds 4e and 4l exhibited the best activity against S. aureus with MIC = 16 µg/L. Compound 4k exhibited the best activity against B. subtilis with MIC = 8 µg/L. Compounds 4o was the most active compounds against C. albicans with MIC = 4 µg/L. CONCLUSION: In-silico predictions were utilized to investigate the structure activity relationship of all the newly synthesized antimicrobial compounds. In this regard, a ligand-based pharmacophore model was developed highlighting the key features required for general antimicrobial activity. While the molecular docking was carried out to predict the most probable inhibition and binding mechanisms of these antibacterial and antifungal agents using the MOE docking suite against few reported target proteins.

3.
J Photochem Photobiol B ; 180: 98-108, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29413708

RESUMO

Owing to their structural novelty and inherent three-dimensionality, spiro scaffolds have been shown indisputable promise as chemopreventive agents. A new series of heterocycles containing spirooxindole and pyrrolidine rings were synthesized by the 1,3-dipolar cycloaddition of an azomethine ylide, which was generated in situ by the condensation of a secondary amino acid (l­proline) and dicarbonyl compounds (isatin), with dipolarophiles. This method is simple and provides diverse and biologically interesting products. The new series of compounds with a high degree of stereo- and regioselectivity were evaluated against breast cancer cell lines (MCF-7) and leukemia (K562). Among them, compound 4g was identified as the most potent with IC50 values of 15.49 ±â€¯0.04 µM, against breast cancer cell lines (MCF-7) compared to standard drug 5-Fu (IC50 = 78.28 ±â€¯0.2 µM) and compound 4i IC50 values of 13.38 ±â€¯0.14 µM against leukemia (K562) compared to standard drug 5-fluorouracil (5-FU) (IC50 = 38.58 ±â€¯0.02). The selective apoptotic effects of 4g were investigated against MCF-12 normal mammary cell and the cytotoxicity of 4g was not associated with any induction of necrosis compared to untreated cells. Molecular docking studies were investigated. From the docking data, these compounds could be act as small molecules that inhibit the MDM2-p53 interaction.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Indóis/química , Simulação de Acoplamento Molecular , Compostos de Espiro/química , Antineoplásicos/metabolismo , Sítios de Ligação , Domínio Catalítico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Reação de Cicloadição , Fluoruracila/farmacologia , Humanos , Células K562 , Células MCF-7 , Conformação Molecular , Proteínas Proto-Oncogênicas c-mdm2/química , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Teoria Quântica , Estereoisomerismo
4.
Des Monomers Polym ; 20(1): 167-176, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29491790

RESUMO

The homopolymerization and copolymerization of styrene and methyl methacrylate, initiated for the first time by the combination of azo-bis-isobutyronitrile (AIBN) with [(SiMes)Ru(PPh3)(Ind)Cl2] complex. The reactions were successfully carried out, on a large scale, in presence this complex at 80 °C. It was concluded from the data obtained that the association of AIBN with the ruthenium complex reduces considerably the transfer reactions and leads to the controlled radical polymerization and the well-defined polymers.

5.
Bioorg Med Chem ; 24(8): 1675-82, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26972921

RESUMO

A series of new malonamide derivatives were synthesized by Michael addition reaction of N(1),N(3)-di(pyridin-2-yl)malonamide into α,ß-unsaturated ketones mediated by DBU in DCM at ambient temperature. The inhibitory potential of these compounds in vitro, against α-glucosidase enzyme was evaluated. Result showed that most of malonamide derivatives were identified as a potent inhibitors of α-glucosidase enzyme. Among all the compounds, 4K (IC50=11.7 ± 0.5 µM) was found out as the most active one compared to standard drug acarbose (IC50=840 ± 1.73 µM). Further cytotoxicity of 4a-4m were also evaluated against a number of cancer and normal cell lines and interesting results were obtained.


Assuntos
Inibidores de Glicosídeo Hidrolases/síntese química , Inibidores de Glicosídeo Hidrolases/farmacologia , Malonatos/síntese química , Malonatos/farmacologia , alfa-Glucosidases/metabolismo , Células 3T3 , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases/química , Humanos , Malonatos/química , Camundongos , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade
6.
Molecules ; 19(11): 17187-201, 2014 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-25347461

RESUMO

An eco-benign synthesis of pyrimidine derivatives 2a,b containing different functional groups with different electronic character starting from nitroalkenes 1a and 2b has been described. The structures for 1a and 2a,b have been characterized by single crystal X-ray diffraction analysis. The thermal data of the molecules pointed towards important structural aspects of their stability. The mechanism of their thermal decomposition is discussed. The thermodynamic parameters of the dissociation steps were evaluated and discussed. DFT calculations reveal that the compound 1a possesses a high calculated dipole moment value (8.28 D) which indicates its high reactivity towards its surrounding molecules.


Assuntos
Pirimidinas/química , Alcenos/química , Eletrônica/métodos , Nitrocompostos/química , Termogravimetria/métodos , Difração de Raios X/métodos
7.
Steroids ; 85: 65-72, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24755238

RESUMO

Biotransformation of the anabolic steroid dianabol (1) by suspended-cell cultures of the filamentous fungi Cunninghamella elegans and Macrophomina phaseolina was studied. Incubation of 1 with C. elegans yielded five hydroxylated metabolites 2-6, while M. phaseolina transformed compound 1 into polar metabolites 7-11. These metabolites were identified as 6ß,17ß-dihydroxy-17α-methylandrost-1,4-dien-3-one (2), 15α,17ß-dihydroxy-17α-methylandrost-1,4-dien-3-one (3), 11α,17ß-dihydroxy-17α-methylandrost-1,4-dien-3-one (4), 6ß,12ß,17ß-trihydroxy-17α-methylandrost-1,4-dien-3-one (5), 6ß,15α,17ß-trihydroxy-17α-methylandrost-1,4-dien-3-one (6), 17ß-hydroxy-17α-methylandrost-1,4-dien-3,6-dione (7), 7ß,17ß,-dihydroxy-17α-methylandrost-1,4-dien-3-one (8), 15ß,17ß-dihydroxy-17α-methylandrost-1,4-dien-3-one (9), 17ß-hydroxy-17α-methylandrost-1,4-dien-3,11-dione (10), and 11ß,17ß-dihydroxy-17α-methylandrost-1,4-dien-3-one (11). Metabolite 3 was also transformed chemically into diketone 12 and oximes 13, and 14. Compounds 6 and 12-14 were identified as new derivatives of dianabol (1). The structures of all transformed products were deduced on the basis of spectral analyses. Compounds 1-14 were evaluated for ß-glucuronidase enzyme inhibitory activity. Compounds 7, 13, and 14 showed a strong inhibition of ß-glucuronidase enzyme, with IC50 values between 49.0 and 84.9 µM.


Assuntos
Biotransformação , Fungos/metabolismo , Metandrostenolona/química , Animais , Caenorhabditis elegans/efeitos dos fármacos , Fungos/enzimologia , Fungos/crescimento & desenvolvimento , Glucuronidase/antagonistas & inibidores , Glucuronidase/metabolismo , Hidroxilação
8.
Int J Mol Sci ; 15(3): 5115-27, 2014 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-24663060

RESUMO

A series of new 2-aminobenzamide derivatives (1-10) has been synthesized in good to excellent yields by adopting both conventional and/or a time-efficient microwave assisted methodologies starting from isatoic anhydride (ISA) and characterized on the basis of their physical, spectral and microanalytical data. Selected compounds of this series were then tested against various bacterial (Bacillus subtilis (RCMB 000107) and Staphylococcus aureus (RCMB 000106). Pseudomonas aeruginosa (RCMB 000102) and Escherichia coli (RCMB 000103) and fungal strains (Saccharomyces cerevisiae (RCMB 006002), Aspergillus fumigatus (RCMB 002003) and Candida albicans (RCMB 005002) to explore their potential as antimicrobial agents. Compound 5 was found to be the most active compound among those tested, which showed excellent antifungal activity against Aspergillus fumigatus (RCMB 002003) more potent than standard Clotrimazole, and moderate to good antibacterial and antifungal activity against most of the other strains of bacteria and fungi. Furthermore, potential pharmacophore sites were identified and their activity was related with the structures in the solution.


Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , ortoaminobenzoatos/síntese química , ortoaminobenzoatos/farmacologia , Anti-Infecciosos/química , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/crescimento & desenvolvimento , Bacillus subtilis/efeitos dos fármacos , Bacillus subtilis/crescimento & desenvolvimento , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Cristalização , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Modelos Químicos , Estrutura Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/crescimento & desenvolvimento , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/crescimento & desenvolvimento , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Relação Estrutura-Atividade , ortoaminobenzoatos/química
9.
ScientificWorldJournal ; 2014: 649197, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24574906

RESUMO

The importance of cooperative hydrogen-bonding effects has been demonstrated using novel 3-methylenecyclopropane-1,2-dicarboxylic acid (Feist's acid (FA)) as hydrogen bond donor catalysts for the addition of indole and pyrrole to trans-ß-nitrostyrene derivatives. Because of the hydrogen bond donor (HBD) ability, Feist's acid (FA) has been introduced as a new class of hydrogen bond donor catalysts for the activation of nitroolefin towards nucleophilic substitution reaction. It has effectively catalyzed the Michael addition of indoles and pyrrole to ß-nitroolefins under optimum reaction condition to furnish the corresponding Michael adducts in good to excellent yields (up to 98%). The method is general, atom-economical, convenient, and eco-friendly and could provide excellent yields and regioselectivities. Some newly synthesized compounds were for examined in vitro antimicrobial activity and their preliminary results are reported.


Assuntos
Alcenos/síntese química , Anti-Infecciosos/síntese química , Ciclopropanos/síntese química , Ácidos Dicarboxílicos/síntese química , Indóis/síntese química , Pirróis/síntese química , Anti-Infecciosos/farmacologia , Bacillus subtilis/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Catálise , Escherichia coli/efeitos dos fármacos , Ligação de Hidrogênio , Staphylococcus aureus/efeitos dos fármacos
10.
Molecules ; 19(1): 1150-62, 2014 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-24445342

RESUMO

An efficient method for the synthesis of a variety of pyrimidine derivatives 3a-t by reaction of barbituric acids 1a,b as Michael donor with nitroalkenes 2a-k as Michael acceptor using an aqueous medium and diethylamine is described. This 1,4-addition strategy offers several advantages, such as using an economic and environmentally benign reaction media, high yields, versatility, and shorter reaction times. The synthesized compounds were identified by 1H-NMR, 13C-NMR, CHN, IR, and MS. The structure of compound 3a was further confirmed by single crystal X-ray structure determination.


Assuntos
Barbitúricos/síntese química , Dietilaminas/química , Nitrocompostos/química , Barbitúricos/química , Técnicas de Química Sintética , Química Verde , Solventes/química , Água/química
11.
Int J Mol Sci ; 14(12): 23762-73, 2013 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-24317435

RESUMO

A simple protocol, involving the green synthesis for the construction of novel bis-pyrimidine derivatives, 3a-i and 4a-e are accomplished by the aqueous diethylamine media promoted tandem Aldol-Michael reaction between two molecules of barbituric acid derivatives 1a,b with various aldehydes. This efficient synthetic protocol using an economic and environmentally friendly reaction media with versatility and shorter reaction time provides bis-pyrimidine derivatives with high yields (88%-99%).


Assuntos
Aldeídos/química , Dietilaminas/química , Pirimidinas/química , Barbitúricos/química , Cristalografia por Raios X , Química Verde , Conformação Molecular , Pirimidinas/síntese química , Água/química
12.
Chem Cent J ; 6(1): 109, 2012 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-23021311

RESUMO

BACKGROUND: Biotransformation by using microbial and plant cell cultures has been applied effectively for the production of fine chemicals on large scale. Inspired by the wealth of literature available on the biotransformation of steroids, we decided to investigate the biotransformation of ethynodiol diacetate (1) by using plant and microbial cultures. RESULTS: The biotransformation of ethynodiol diacetate (1) with Cunninghamella elegans and plant cell suspension cultures of Ocimum basilicum and Azadirachta indica is being reported here for the first time. Biotransformation of 1 with Cunninghamella elegans yielded three new hydroxylated compounds, characterized as 17α-ethynylestr-4-en-3ß,17ß-diacetoxy-6α-ol (2), 17α-ethynylestr-4-en-3ß,17ß-diacetoxy-6ß-ol (3), and 17α-ethynylestr-4-en-3ß,17ß-diacetoxy-10ß-ol (4) and a known metabolite, 17α-ethynyl-17ß-acetoxyestr-4-en-3-one (5). The biotransformation of 1 with Ocimum basilicum included hydrolysis of the ester group, oxidation of alcohol into ketone, and rearrangement of the hydroxyl group. Thus four major known metabolites were characterized as 17α-ethynyl-17ß-acetoxyestr-4-en-3-one (5), 17α-ethynyl-17ß-hydroxyestr-4-en-3-one (6), 17α-ethynyl-3 ß-hydroxy-17ß-acetoxyestr-4-ene (7) and 17α-ethynyl-5α,17ß-dihydroxyestr-3-ene (8). Biotransformation of 1 with Azadirachta indica culture yielded compounds 5 and 6. Spectroscopic data of compound 8 is being reported for the first time. Structure of compound 6 was unambiguously deduced through single-crystal x-ray diffraction studies. CONCLUSION: Biotransformation of an oral contraceptive, ethynodiol diacetate (1), by using microbial and plant cell cultures provides an efficient route to the synthesis of a library of new steroids with potential contraceptive properties. These methods can be employed in the production of such compounds with high stereoselectivity.

13.
Int J Mol Sci ; 13(5): 5542-5553, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22754314

RESUMO

An efficient and convenient strategy for the enantioselective synthesis of enantiomerically enriched 10-ethyl-7,8-dihydro-γ-ionone isomers (R)-(+)-7, and (S)-(-)-7 are described utilizing a lipase mediated resolution protocol, and reductive elimination of the secondary allylic alcohol as the key step. The enantioselective and diastereoselective lipase kinetic acetylation of 4-hydroxy-γ-ionone derivatives 6a afforded the 4-acetyl-γ-ionone derivatives (-)-8, and the 4-hydrox-γ-ionone derivatives (+)-6a, which are suitable precursors of the desired products. Stereospecific palladium-mediated elimination of allylic acetate provides the target compounds with an excellent enantiomeric excess and yield. Additionally, the novel 4,5-didehydro-α-ionone 13 is obtained from readily prepared (2,6,6-trimethylcyclohexa-2,4-dien-1-yl) methanol 9. The structures of all newly synthesized compounds have been elucidated by (1)H, (13)C NMR, GC-MS, and IR spectrometry. These compounds represent a new class of odorants that may be of pivotal relevance in industrial perfumery.


Assuntos
Norisoprenoides/síntese química , Isomerismo , Lipase/metabolismo , Norisoprenoides/química , Norisoprenoides/metabolismo , Oxirredução , Pseudomonas/enzimologia
14.
Molecules ; 17(5): 5550-63, 2012 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-22572937

RESUMO

The hemilabile chiral C2 symmetrical bidentate substituted amide ligands (1R,2R)-5(a-d) and (1S,2S)-6(a-d) were synthesized in quantitative yield from (1R,2R)-(+)-3-methylenecyclo-propane-1,2-dicarboxylic acid (1R,2R)-3 and (1S,2S)-(-)-3-methylene-cyclopropane-1,2-dicarboxylic acid (1S,2S)-3, in two steps, respectively. The chiral Feist's acids (1R,2R)-3 and (1S,2S)-3 were obtained in good isomeric purity by resolution of trans-(±)-3-methylene-cyclopropane-1,2-dicarboxylic acid from an 8:2 mixture of tert-butanol and water, using (R)-(+)-α-methylbenzyl amine as a chiral reagent. This process is reproducible on a large scale. All these new synthesized chiral ligands were characterized by 1H-NMR, 13C-NMR, IR, and mass spectrometry, as well as elemental analysis and their specific rotations were measured. These new classes of C2 symmetric chiral bisamide ligands could be of special interest in asymmetric transformations.


Assuntos
Amidas/síntese química , Ciclopropanos/síntese química , Ácidos Dicarboxílicos/síntese química , Fenetilaminas/química , Ciclopropanos/química , Ácidos Dicarboxílicos/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estereoisomerismo , Água/química , terc-Butil Álcool/química
15.
Int J Mol Sci ; 13(2): 2263-2275, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22408452

RESUMO

A comprehensive and facile method for the synthesis of new functionalized bis-heterocyclic compounds containing a thieno[2,3-b]thiophene motif is described. The hitherto unknown bis-pyrazolothieno[2,3-b]thiophene derivatives 2a-c, bis-pyridazin othieno[2,3-b]thiophene derivatives 4, bis-pyridinothieno[2,3-b]thiophene derivatives 6a,b, and to an analogous bis-pyridinothieno[2,3-b]thiophene nitrile derivatives 7 are obtained. Additionally, the novel bis-pyradazinonothieno[2,3-b]thiophene derivatives 9, and nicotinic acid derivatives 10, 11 are obtained via bis-dienamide 8. The structures of all newly synthesized compounds have been elucidated by (1)H, (13)C NMR, GCMS, and IR spectrometry. These compounds represent a new class of sulfur and Nitrogen containing heterocycles that should also be of interest as new materials.


Assuntos
Compostos Heterocíclicos/síntese química , Tiofenos/síntese química , Compostos Heterocíclicos/química , Espectroscopia de Ressonância Magnética , Ácidos Nicotínicos/síntese química , Ácidos Nicotínicos/química , Nitrilas/síntese química , Nitrilas/química , Nitrogênio/química , Enxofre/química , Tiofenos/química
16.
Planta Med ; 78(3): 269-75, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22174076

RESUMO

Salvialeriafone (1), a novel diterpene-norditerpene conjugate, was isolated from Salvia leriaefolia. Additionally, two new abietane-type diterpenoids, salvialerial (2) and salvialerione (3), as well as four known compounds, sugiol (4), salvicanaric acid (5), dehydroroyleanone (6), and cariocal (7), were isolated and identified. Their structures were determined by spectroscopic data analyses. Known compounds were isolated from this plant for the first time. Compounds 1, 5, 6, and 7 exhibited IN VITRO antiproliferative activity against the human cervical cancer cell line (Hela), while 6 showed cytotoxicity against the human prostate cancer cell line (PC3).


Assuntos
Diterpenos/química , Salvia/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Células HeLa , Humanos , Irã (Geográfico) , Masculino , Estrutura Molecular , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Neoplasias da Próstata/tratamento farmacológico
17.
Planta Med ; 77(16): 1829-34, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21766268

RESUMO

Three new cycloartane triterpenoids have been isolated from Astragalus bicUSPIS Fisch. Their structures were elucidated as 23(R),24(S),25( R),26(S)-16 ß/23,23/26,24/25-triepoxy-26-hydroxy-9,19-cyclolanosta-3,6-dione (1), 6 α,23,24,25-tetraol-16 ß-acetoxy-23(R),24(R)-9,19-cyclanosta-3-one (2), and 6 α,23,24,25-tetraol-16 ß-acetoxy-23(R),24(R)-9,19-cyclolanosta-3 ß- O-xyloside (3), based on their spectroscopic analysis. All cycloartane tritepenoids exhibited weak cytotoxicities against 3T3 fibroblast cells as compared to the standard drug cycloheximide. Compounds 3 and 4 were also tested for their antileishmanial potential, and a weak activity was observed against promastigotes of Leishmania major.


Assuntos
Antiprotozoários/isolamento & purificação , Astrágalo/química , Extratos Vegetais/isolamento & purificação , Triterpenos/isolamento & purificação , Animais , Antiprotozoários/química , Antiprotozoários/farmacologia , Sobrevivência Celular , Relação Dose-Resposta a Droga , Concentração Inibidora 50 , Leishmania major/efeitos dos fármacos , Medicina Tradicional , Camundongos , Estrutura Molecular , Células NIH 3T3 , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Triterpenos/química , Triterpenos/farmacologia
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