RESUMEN

The present investigation was intended to characterize pigments for the first time from Rhodotorula taiwanensis (LC011412) yeast isolated from the ethic fermentation starter culture source meant to evaluate its carotenoid contents for beneficial applications. The pigments were extracted by an optimized solvent system, purified by flash chromatography and were identified by TLC and UV/VIS spectroscopy. The absorbance spectra confirmed the presence of ß-carotene, ß-cryptoxanthin, torulene and torularhodin that showed maximum absorbance (λmax ) within the ranges. The fractions were further characterized by LC/MS and analyzed through FT-IR and NMR for structure elucidation. Spectral analyses also confirmed the presence of the compounds mentioned above. These compounds promise great commercial value and could be useful for large scale production anticipated for potential applications in food, nutraceutical, pharmaceutical and cosmetic sectors. It is pertinent that the characterized carotenoid pigments from the isolate have incredible prospects in industrial applications which require profound attention.

Asunto(s)

beta-Criptoxantina/química , Carotenoides/química , Rhodotorula/metabolismo , Levaduras/aislamiento & purificación , Cromatografía Liquida/métodos , Espectroscopía de Resonancia Magnética/métodos , Espectrometría de Masas/métodos , Espectroscopía Infrarroja por Transformada de Fourier

RESUMEN

Breast Cancer (BCa) is the most often diagnosed cancer among women who were in the late 1940's. Breast cancer growth is largely dependent on the expression of estrogen and progesterone receptor. Breast cancer cells may have one, both, or none of these receptors. The treatment for breast cancer may involve surgery, hormonal therapy (Tamoxifen, an aromatase inhibitor, etc.) and oral chemotherapeutic drugs. The molecular docking technique reported the findings on the potential binding modes of the 2-(2-bromo-3-nitrophenyl)-5-phenyl-1,3,4-oxadiazole derivatives with the estrogen receptor (PDB ID: 3ERT). The 1,3,4-oxadiazole derivatives 4a-4j have been synthesized and described by spectroscopic method. 2-(2-Bromo-6-nitrophenyl)-5-(4-bromophenyl)-1,3,4-oxadiazole (4c) was reconfirmed by single-crystal XRD. All the compounds have been tested in combination with generic Imatinib pharmaceutical drug against breast cancer cell lines isolated from Caucasian woman MCF-7, MDA-MB-453 and MCF-10A non-cancer cell lines. The compounds with the methoxy (in 4c) and methyl (in 4j) substitution were shown to have significant cytotoxicity, with 4c showing dose-dependent activation and decreased cell viability. The mechanism of action was reported by induced apoptosis and tested by a DNA enzyme inhibitor experiment (ELISA) for Methyl Transferase. Molecular dynamics simulations were made for hit molecule 4c to study the stability and interaction of the protein-ligand complex. The toxicity properties of ADME were calculated for all the compounds. All these results provide essential information for further clinical trials.

Asunto(s)

Antineoplásicos/síntesis química , Diseño de Fármacos , Oxadiazoles/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Sitios de Unión , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , ADN (Citosina-5-)-Metiltransferasa 1/antagonistas & inhibidores , ADN (Citosina-5-)-Metiltransferasa 1/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/farmacología , Receptor alfa de Estrógeno/química , Receptor alfa de Estrógeno/metabolismo , Femenino , Humanos , Mesilato de Imatinib/farmacología , Conformación Molecular , Simulación del Acoplamiento Molecular , Oxadiazoles/metabolismo , Oxadiazoles/farmacología , Relación Estructura-Actividad

RESUMEN

[This corrects the article DOI: 10.3389/fchem.2019.00474.].

RESUMEN

Prostate Cancer (PCa) is the most frequently diagnosed cancer in men in their late '50s. PCa growth is mainly due to the activation of the androgen receptor by androgens. The treatment for PCa may involve surgery, hormonal therapy, and oral chemotherapeutic drugs. A structural based molecular docking approach revealed the findings of (E)-N'-((1-chloro-3,4-dihydronaphthalen-2-yl)methylene)benzohydrazide derivatives, where the possible binding modes of the compounds with protein (PDB ID: 3V49) are shown. The compounds (6a-k) were synthesized and characterized by using conventional methods. The compounds, 6g, 6j, and 6k were reconfirmed through single crystal X-ray diffraction (XRD). Further, the compounds (6a-k) and standard drug were evaluated against human prostate cancer cell lines, LNCaP and PC-3 and the non-cancerous cell line, 3T3. Among these compounds, 6g and 6j showed higher cytotoxicity, and 6g exhibited dose-dependent activity and reduced cell viability. The mechanism of action was observed through the induced apoptosis and was further confirmed by western blot and ELISA. Molecular dynamics simulation studies were carried out to calculate the interaction and the stability of the protein-ligand complex in motion. ADME properties were predicted for all the tested compounds. These findings may give vital information for further development.

RESUMEN

AIM AND OBJECTIVE: To study the structural difference, optimization, molecular docking and development of new benzoyl amino phenoxy phenol derivatives as anti-prostate cancer agents. MATERIALS AND METHODS: Strategies towards the identification of novel benzoyl amino phenoxy phenol (BAPP), molecular docking was performed with the designed Androgen Receptor (AR) blockers. Pharmacophore-based studies revealed that the nitro- or cyano-substituted anilide groups have influenced the activity profiles of non-steroidal AR antagonists, followed by the molecular docking studies with five AR receptors. Molecular docking studies were carried out using Maestro from Schrödinger. Absorption, Distribution, Metabolism, and Excretion (ADME) properties of the BAPP derivatives were evaluated for the predictive bioavailability/drug-likeness. These studies supported vital information for designing new anti-prostate cancer agents. RESULTS AND DISCUSSION: There are 125 compounds were screened and best fit compounds (12 entries) were well-synthesized in good to excellent yields and anticancer activities were evaluated. The compounds, 6i showed the highest activities of this series (14.65 ± 1.35 µM). CONCLUSION: The present approach is simple and efficient for the synthesis of BAPP derivatives and the observed IC50 values of BAPPs were in good agreement with the glide scores obtained from the molecular docking. We, further, intend to carry out in vitro and in vivo AR binding studies for the active compounds.

Asunto(s)

Antagonistas de Receptores Androgénicos/química , Antineoplásicos/química , Simulación del Acoplamiento Molecular , Fenol/farmacología , Simulación por Computador , Diseño de Fármacos , Humanos , Masculino , Fenol/síntesis química , Neoplasias de la Próstata/tratamiento farmacológico

RESUMEN

Emerging evidence present credible support in favour of the potential role of mahanine and girinimbine. Non-toxic herbal carbazole alkaloids occur in the edible part of Murraya koenigii, Micromelum minutum, M. zeylanicum, and M. euchrestiolia. Mahanine and girinimbine are the major potent compounds from these species. In fact, they interfered with tumour expansion and metastasis development through down-regulation of apoptotic and antiapoptotic protein, also involved in the stimulation of cell cycle arrest. Consequently, these compounds were well proven for the in-vitro and in vivo evaluation that could be developed as novel agents either alone or as an adjuvant to conventional therapeutics. Therefore, mahanine and girinimbine analogs have the potential to be the promising chemopreventive agents for the tumour recurrence and the treatment of human malignancies. In this review, an updated wide-range of pleiotropic anticancer and biological effects induction by mahanine and girinimbine against cancer cells were deeply summarized.

Asunto(s)

Alcaloides/química , Antineoplásicos/farmacología , Carbazoles/química , Alcaloides/farmacología , Antineoplásicos/química , Carbazoles/farmacología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Humanos

RESUMEN

AIM: To synthesize a series of new thiazolidinone-pyrazole hybrids (5a-o) and assess their anticancer (in vitro and in vivo) and antimicrobial activities. RESULTS: The compounds 5h (against Ehrlich ascites carcinoma cells), 5e and 5i (against the human breast cancer [MDA-MB231] cell line) exhibited potent anticancer activity. All the compounds except 5g and 5e found to be less toxic for the human dermal fibroblast cells. The effective interactions of the compounds in silico with MDM2 exemplified their inhibitory potency. The derivatives also showed moderate antimicrobial activity. CONCLUSION: The halogen atoms on various positions of the N-arylamino ring played an advantageous role in elevating the potency of the molecules. Thus, these conjugates could be used as a lead for further optimization to achieve promising therapeutics.

Asunto(s)

Antiinfecciosos/química , Antineoplásicos/química , Pirazoles/química , Tiazolidinas/química , Animales , Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Antiinfecciosos/uso terapéutico , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Candida albicans/efectos de los fármacos , Candidiasis/tratamiento farmacológico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Ratones , Simulación del Acoplamiento Molecular , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Pirazoles/síntesis química , Pirazoles/farmacología , Pirazoles/uso terapéutico , Relación Estructura-Actividad , Tiazolidinas/síntesis química , Tiazolidinas/farmacología , Tiazolidinas/uso terapéutico

RESUMEN

Design of highly efficient phosphorescent emitters based on metal- and heavy atom-free boron compounds has been demonstrated by taking advantage of the singlet fission process. The combination of a suitable molecular scaffold and appropriate electronic nature of the substituents has been utilized to tailor the phosphorescence emission properties in solution, neat solid, and in doped PMMA thin films.

RESUMEN

Thrombin plays a key role in the regulation of hemostasis and thrombosis. Inhibition of thrombin is therefore an effective therapeutic target to prevent the formation of blood clots and related thromboembolism disorders. Hence, we have developed chemical feature based pharmacophore models of thrombin inhibitors. The best hypothesis, Hypo1, is characterized with two hydrogen bond acceptors (A), one hydrophobic (H) and one ring aromatic (R) feature. Hypo1 was cross validated using several techniques to prove its validity and statistical significance. The well validated model Hypo1 was used as a 3D query to perform virtual screening. The scores obtained from virtual screening were sorted by applying drug-like filters and molecular docking studies. Finally, 4 compounds were obtained as drug-like leads based on scoring functions, binding modes and molecular interactions at the active site. These 4 molecules were further optimized by adding different substitutions in their side chains. When compared to the original database hits, optimized molecules showed high scoring function, good binding modes and molecular interactions. Hence, we suggest that, upon optimization, these four database hits can act as potential virtual leads to design novel thrombin inhibitors. Also, our model could be useful to retrieve the structurally diverse compounds from various databases.

Asunto(s)

Diseño de Fármacos , Inhibidores de Proteasas/química , Inhibidores de Proteasas/farmacología , Trombina/antagonistas & inhibidores , Dominio Catalítico , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Relación Estructura-Actividad , Trombina/química , Trombina/metabolismo

RESUMEN

A series of 1-allyl-2,6-diphenylpiperidin-4-one oximes 17-24 and 1-allyl-2,6-diphenylpiperidin-4-one O-benzyloximes 25-32 were synthesized from respective 1-allyl-2,6-diphenylpiperidin-4-ones 9-16. The structure and the conformations have been investigated for all the synthesized compounds 9-32 by analytical and spectral techniques (IR, Mass, 1H, 13C, 2D NMR and X-ray Diffraction). Based on the proton NMR analysis, all the synthesized compounds 9-32, exposed chair conformation except compounds 22 and 30 (twist boat conformation). For all the synthesized compounds 9-32 antimicrobial activity has been carried out against a panel of selected bacterial and fungal strains using Streptomycin and Amphotericin B as standards. Antibacterial and antifungal activity of compounds 19, 21, 23 (allyl oximes) 25-29, 31, 32 (allyl oxime ethers) and 11, 13 (ketones) exerted moderate to excellent activity against Staphylococcus aureus, Bacillus subtilis, Salmonella typhi bacterial strains and Penicillium chrysogenum, Aspergillus niger, Fusarium oxysporum fungal strains. The MIC results of all the synthesized compounds revealed that most of the oxime ether compounds exhibit excellent activity against selected bacterial and fungal strains.

Asunto(s)

Bacterias/efectos de los fármacos , Diseño de Fármacos , Éteres/química , Hongos/efectos de los fármacos , Oximas/química , Piperidonas , Compuestos Alílicos/síntesis química , Compuestos Alílicos/química , Compuestos Alílicos/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Antifúngicos/farmacología , Éteres/síntesis química , Éteres/farmacología , Pruebas de Sensibilidad Microbiana , Conformación Molecular , Oximas/síntesis química , Oximas/farmacología , Piperidonas/síntesis química , Piperidonas/química , Piperidonas/farmacología

RESUMEN

The synthesis, photophysical, and electrochemical attributes of a novel class of boron difluorides containing an aromatic-fused alicyclic/hetero-alicyclic ring built on a ß-iminoenamine chromophoric backbone are reported. The compounds displayed large Stokes shifts (86-121 nm), and were emissive in the solid state. The quantum yields obtained in solution at room temperature were unusually lower by an order of magnitude compared to those in the solid state. Some of the tested compounds displayed aggregation-induced emission (AIE). Single crystal XRD analyses revealed a lack of interplanar π-π interactions, which are presumed to be absent owing to non-planarity of the alicyclic component in the molecule. For most of the studied compounds, time-dependent DFT (TD-DFT) calculations invariably reveal intramolecular charge transfer (π-π*) characteristics with the frontier orbitals concentrated on the boron-nitrogen heterocycle. The participation of boron and fluorine atoms was found to be negligible.

RESUMEN

2-[(2,4-Diaryl-3-azabicyclo[3.3.1]nonan-9-ylidene)hydrazono]-4-phenyl-2,3-dihydrothiazoles (3a-3k) have been synthesized by the cyclization of 2-[(2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one thiosemicarbazones with phenacyl bromide and characterized by analytical (melting point and elemental analysis) and spectral (IR, (1)H NMR, (13)C NMR, D(2)O exchange, NOESY and mass) techniques. The novel Hantzsch products (3a-3k) were screened for their in vitro antibacterial and antifungal activities against some selected microorganisms. Structure activity relationship (SAR) for the reported compounds was studied by comparing their MIC values with standard drugs (Streptomycin and Amphotericin B). The results show that 3e against Escherichia coli and Cryptococcus neoformans3i against Bacillus Subtilis, 3b against Aspergillus flavus, and 3k against Rhizopus sp. were found to show significant growth inhibition.

Asunto(s)

Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Compuestos de Azabiciclo/síntesis química , Compuestos de Azabiciclo/farmacología , Antiinfecciosos/química , Aspergillus flavus/efectos de los fármacos , Compuestos de Azabiciclo/química , Bacillus subtilis/efectos de los fármacos , Cryptococcus neoformans/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Rhizopus/efectos de los fármacos , Estereoisomerismo

RESUMEN

In the title compound, C(28)H(35)N(3)O(4), the piperidine ring adopts a boat conformation while the piperazine ring adopts a chair conformation with an equatorial orientation of the phenyl groups. The dihedral angle between the mean planes of the benzene rings is 74.14 (8)°. The mol-ecular conformation is stabilized by a weak intra-molecular C-H⋯N inter-action and the crystal packing is stabilized by weak inter-molecular C-H⋯O inter-actions.

RESUMEN

New series of 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one 4'-phenylthiosemicarbazones (compounds 9-16) was obtained from the corresponding 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones. The synthesized compounds have been characterized by their elemental, analytical, and spectral studies. Besides, these reported compounds were screened for their antibacterial and antifungal activities against a spectrum of microbial organisms. These studies proved that against bacteria, compounds 10 and 11 against Bacillus subtilis, compound 13 against Salmonella typhi, show maximum inhibition potency at low concentration (6.25 µg/mL), whereas against fungal, compounds 11, 13, and 16 against Candida albicans and compounds 12 and 13 against Cryptococcus neoformans, showed beneficial antifungal activity at minimum concentration (6.25 µg/mL).

Asunto(s)

Antibacterianos/farmacología , Antifúngicos/farmacología , Bacterias/efectos de los fármacos , Hongos/efectos de los fármacos , Tiosemicarbazonas/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antifúngicos/síntesis química , Antifúngicos/química , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Estereoisomerismo , Relación Estructura-Actividad , Tiosemicarbazonas/síntesis química , Tiosemicarbazonas/química

RESUMEN

In an attempt to find a new class of antimicrobial agents, a series of new 1,3,4-thiadiazolines were synthesized from 2,6-diarylpiperidin-4-ones, via the corresponding 4'-phenylthiosemicarbazones. All the synthesized compounds (23-39) were virtually screened against bacterial (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi) and fungal strains (Candida albicans, Rhizopus sp, Aspergillus niger and Aspergillus flavus) by serial dilution method. QSAR study indicated that the increase in weakly polar component of solvent accessible surface area will favour antibacterial activity while increase in polarizability and decrease in ionisation potential and hydrogen bond donor will favour antifungal activity.

Asunto(s)

Antiinfecciosos/síntesis química , Relación Estructura-Actividad Cuantitativa , Tiadiazoles/farmacología , Antibacterianos , Antiinfecciosos/farmacología , Antifúngicos , Bacterias/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Hongos/efectos de los fármacos , Piperidinas , Electricidad Estática , Tiadiazoles/química

RESUMEN

A small library of diversely substituted 2,4,6,8-tetraaryl-3,7-diazabicyco[3.3.1]nonan-9-ones, their oximes and O-methyloximes were achieved in a stereocontrolled manner by an easiest synthetic strategy as single isomers with high yields. Stereochemistry of all the synthesized compounds was established by their 1D/2D NMR spectral studies, further, witnessed by single-crystal XRD analysis. Accordingly, the compounds exist in a chair-boat conformation with equatorial orientation of the substituents in the chair part and boat-axial orientation in the boat part. Finally, all the synthesized oximes and oxime ethers were evaluated for their in vitro antimicrobial activity against a panel of pathogenic bacteria and fungi, and as a result of the structure-activity correlations, some lead molecules were known for further optimization.

Asunto(s)

Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/síntesis química , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Oximas/química , Antiinfecciosos/química , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Cristalografía por Rayos X , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Estereoisomerismo

RESUMEN

Two series of bicyclic oxime ethers viz, 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one O-benzyloximes 13-24 and 2,4,6,8-tetraaryl-3,7-diazabicyclo[3.3.1]nonan-9-one O-benzyloximes 31-36 were synthesized and stereochemistry was established by their spectral (1D and 2D NMR) and crystal studies. Synthesized oxime ethers were screened for their in vitro antimicrobial activity against a set of pathogenic bacteria (Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhi, Escherichia coli and Klebsiella pneumoniae) and fungi (Candida albicans, Candida-51, Rhizopus sp., Aspergillus niger and Aspergillus flavus) by twofold serial dilution method, respectively, using Ciprofloxacin and Amphotericin B as standards. Most of the molecules expressed promising antimicrobial profile against the tested pathogens and even a few compounds 16, 21, 22, 33 and 34 were better than standard drugs.

Asunto(s)

Antibacterianos/química , Antifúngicos/química , Compuestos Bicíclicos con Puentes/química , Éteres/química , Oximas/química , Antibacterianos/síntesis química , Antibacterianos/farmacología , Antifúngicos/síntesis química , Antifúngicos/farmacología , Bacterias/efectos de los fármacos , Compuestos Bicíclicos con Puentes/síntesis química , Compuestos Bicíclicos con Puentes/farmacología , Éteres/síntesis química , Éteres/farmacología , Hongos/efectos de los fármacos , Oximas/síntesis química , Oximas/farmacología

RESUMEN

Three series of oxime ethers viz, 2,6-diarylpiperidin-4-one O-benzyloximes 5a-o, 2,6-diaryltetrahydropyran-4-one O-benzyloximes 7a-e and 2,6-diaryltetrahydrothiopyran-4-one O-benzyloximes 11a-b and 12a-c were synthesized and stereochemistry is established by their spectral and single crystal analysis. A SAR study has been carried out for the above oxime ethers against a panel of antibacterial (Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhi and Escherichia coli) and antifungal agents (Candida albicans, Candida-51, Rhizopus sp., Aspergillus niger, Aspergillus flavus and Cryptococcus neoformans), respectively, using Ciprofloxacin and Amphotericin B as standards. Most of the chloro/methyl/methoxy substituted compounds exerted moderate to good activity against all the tested organisms; moreover, some compounds (5i, 5l, 5n, 5o, 7c2, 7d1, 7d2, 7e, 11b and 12c) exhibited promising activity than standard drugs.

Asunto(s)

Antibacterianos/síntesis química , Antifúngicos/síntesis química , Éteres/síntesis química , Compuestos Heterocíclicos/síntesis química , Oximas/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Cristalografía por Rayos X , Éteres/química , Éteres/farmacología , Compuestos Heterocíclicos/química , Compuestos Heterocíclicos/farmacología , Pruebas de Sensibilidad Microbiana , Nitrógeno/química , Oximas/química , Oximas/farmacología , Oxígeno/química , Estereoisomerismo , Azufre/química

RESUMEN

The raise in clinical significance of multidrug-resistant bacterial pathogens has directed us to synthesize 2,6-diarylpiperidin-4-one and Delta(3)-tetrahydropyridin-4-ol based benzimidazole and O-arylsulfonyl derivatives. X-ray crystal structure of tetrahydropyridinol (23) confirmed a change in conformation and orientation of substituents upon amide formation. Antibacterial activities evaluated against a wide number of bacterial pathogens (both sensitive and multidrug-resistant) revealed that 19, 27 against Staphylococcus aureus, 27 against Enterococcus faecalis, and 19, 21, 23, and 27 against Enterococcus faecium are significantly good at lowest MIC(90) (16 microg/mL). Inhibitory power noticed by 23 against Vancomycin-Linezolid-resistant E. faecalis and 27 against Vancomycin-resistant E. faecium are onefold better than the standard Linezolid and Trovafloxacin drugs, respectively. Moreover, antitubercular activity for the selected compounds against Mycobacterium tuberculosis H37Rv revealed that compounds 23, 24, and 27 expressed onefold improved potency compared to the standard Rifampicin drug.

Asunto(s)

Antibacterianos/síntesis química , Antituberculosos/síntesis química , Piperidinas/química , Piperidonas/química , Piridinas/química , Antibacterianos/farmacología , Antituberculosos/farmacología , Química Farmacéutica/métodos , Cristalografía por Rayos X/métodos , Diseño de Fármacos , Farmacorresistencia Microbiana , Humanos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Modelos Químicos , Modelos Moleculares , Rifampin/síntesis química , Rifampin/farmacología

RESUMEN

The (1)H and (13)C NMR spectra of 2,4,6,8-tetraaryl-3,7-diazabicyclo[3.3.1]nonan-9-ones (1-2), oximes (3-8) and O-benzyl oximes (9-12) were recorded. The chemical shifts were unambiguously assigned using 1D and 2D NMR spectral data. The results clearly indicate that the compounds exist in chair-boat conformation with equatorial and axial orientation of the aryl groups in the chair and boat forms, respectively. Since the molecules are flexible and dynamic in solution, the chair and boat forms are mutually interconvertible. In 3-12, because of the effect of oximation/oximination, all the protons in the heterobicyclic systems gave distinct signals except the benzylic protons of the boat form. In all synthesized compounds, the aryl group protons at C-6,8 are shielded by the aryl groups at C-2,4 and therefore appear in the lower frequency region than the aryl groups at C-2,4.