RESUMO
A series of twenty one Schiff bases based on boronate ester of 1,2-O-isopropylidene-α-d-xylofuranose scaffold were designed and synthesized by condensation of formyl or amino phenyl boronate esters with substituted anilines or 2-hydroxybenzaldehydes, respectively. All the imines are remarkably stable crystalline solids and were obtained in good yields. All the products were fully characterized by FT-IR, multinuclear NMR ((1)H, (13)C and (11)B) spectroscopy, and elemental analysis. Furthermore, the molecular structures of two of the Schiff bases were established by single crystal X-ray diffraction analysis. All the compounds have been screened for in vitro antimicrobial activity against various Gram-positive and Gram-negative bacterial and fungal strains. They exhibited moderate to good inhibitory activity against most of the tested organisms in comparison with standard drugs.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Monossacarídeos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antifúngicos/síntese química , Antifúngicos/química , Ácidos Borônicos/química , Ácidos Borônicos/farmacologia , Relação Dose-Resposta a Droga , Ésteres/química , Ésteres/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Monossacarídeos/síntese química , Monossacarídeos/química , Bases de Schiff/síntese química , Bases de Schiff/química , Bases de Schiff/farmacologia , Relação Estrutura-AtividadeRESUMO
Thiophene containing "two-wall" aryl extended calix[4]pyrroles were synthesized for the first time, through acid catalyzed condensation of 2-acetylthiophenes with pyrrole. Isomeric "two-walled" calix[4]pyrroles (8a-10a and 8b-10b) were obtained in satisfactory yields and their halide anion binding strengths were investigated in the solution phase by (1)H NMR and in the gas phase by computational methods and mass spectrometry. Change in the chemical shifts of thiophene -CH-protons during the course of NMR titrations entailed participation of the thiophene rings in anion binding; this fact was further substantiated by computational methods. The α,α-(cis)-isomers (8a, 9a, and 10a) showed strong binding toward F(-) and Cl(-) anions when compared to their isomeric α,ß-(trans)-isomer (8b, 9b, and 10b). In both isomers, binding with F(-) anion was found to be stronger than that with Cl(-) anion. Both the solution-phase and gas-phase results revealed that the thiophene rings stabilize the anions through anion-π interactions.
Assuntos
Ânions/química , Calixarenos/química , Porfirinas/química , Tiofenos/química , Tiofenos/síntese química , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Pirróis/química , EstereoisomerismoRESUMO
Two flexible Tröger's base ditopic receptors C4TB and C5TB incorporating monoaza crown ether were designed and synthesized for bisammonium ion complexation. A comprehensive study of host-guest interactions was established by (1)H NMR spectroscopy and DFT calculations. Bisammonium chloride (A1) with a shorter alkyl chain spacer showed the highest affinity for the receptors. M06-2X/cc-pVTZ calculations including the solvent effects on host-guest complexes were employed to explain and rationalize the experimental trends. The short N-H···O or N-H···N hydrogen-bond distances observed in the range of 1.71-1.98 Å indicate the existence of a strong charge assisted hydrogen bonding between the host and the guest. The unusual behaviour (higher binding constant) of A5 in (1)H NMR titration is traced to the conformational folding of the guest.
Assuntos
Éteres de Coroa/química , Éteres de Coroa/síntese química , Desenho de Fármacos , Teoria Quântica , Compostos de Amônio/química , Técnicas de Química Sintética , Ligação de Hidrogênio , TermodinâmicaRESUMO
The present study is aimed at the design and synthesis of peptides with hybrid helix-turn-helix (HTH) motif and their conformational analysis (NMR, MD, and CD studies). The requisite peptides with heterogeneous backbones were prepared from ß-, γ-, and δ-amino acids with carbohydrate side chains and α-amino acid, L-Ala. The α/ß-peptides were prepared from (S)-ß-Caa(l) (C-linked carbo-ß-amino acid with D-lyxo furanoside side chain) and L-Ala with a 1:1 alternation. The α/ß-peptides with "helix-turn" motif displayed a 11/9-helix nucleating a 13-atom H-bonding turn. The α/ß-octapeptides showed the presence of HTH structures with bifurcated 11/15-H-bonded turn. Further, the α/ß-hexapeptide with HT motif, independently on coupling with γ/α/γ/α- and δ/α/δ/α-tetrapeptides at the C-terminus provided access to the decapeptides with "hybrid HTH" motifs. The decapeptide ("α-ß-α-ß-α-ß-γ-α-γ-α") showed a hybrid HTH with "11/9/11/9/11/16/9/12/10" H-bonding, while the decapeptide ("α-ß-α-ß-α-ß-δ-α-δ-α") revealed the presence of a "11/9/11/9/11/17/9/13/11" helical pattern. The above peptides thus have shown compatibility between different types of helices and serendipitous bifurcated 11/16- and 11/17-turns. The present study thus provided the first opportunity for the design and study of "hybrid HTH" motifs with more than one kind of helical structures in them.
Assuntos
Oligopeptídeos/síntese química , Peptídeos/síntese química , Dicroísmo Circular , Sequências Hélice-Volta-Hélice , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Conformação Molecular , Oligopeptídeos/química , Peptídeos/química , Estrutura Terciária de Proteína , EstereoisomerismoRESUMO
A new series of Schizandrin (1) derivatives were synthesized utilizing the C-9 position of the Schizandrin core and evaluated for their cytotoxic activities against HeLa (cervical cancer), A549 (lung cancer), MCF-7 (breast cancer) and DU-145 (prostate cancer) cell lines. Among the synthesized series, 4e, 4f, 4g and 5 showed potent activities against tested cell lines. More significantly, compound 5 exhibited most potent cytotoxic activity against DU-145 with an IC50 value of 1.38⯵M which is comparable to the standard agent, doxorubicin. Further, flow cytometry analysis indicated that 5 arrested cells in G2/M phase and consequently leading to apoptosis. Molecular docking analysis showed that 5 occupied the colchicine binding pocket of tubulin. Overall, the present study demonstrates that 5, as a mitotic-agent.