Ecofriendly Synthesis in Aqueous Medium: An Expeditious Approach to New N,N-Diethyl Amide Bearing Benzenemethanesulfonamides

An highly expeditious synthetic approach for the synthesis of benzenemethanesulfonamides (1a-k) and their new corresponding N,N-diethyl substituted amido moieties (2a-k) has been achieved in aqueous medium at room tem-perature. The reaction condition was thoroughly optimized thereby allowing significant rate enhancement and resulting into excellent yields. The chemical structures of the successful candidates were confirmed using elemental analytical and spectroscopic data such as IR, 1H NMR, 13C NMR and some selected mass spectral dat

Docetaxel-based chemotherapy in the treatment of gastric cancer

Docetaxel-based chemotherapy appears to have considerable promise in advanced gastric cancer. In phase II studies of single agent docetaxel, response rates (RRs) of 17% to 24% have been achieved in previously untreated patients. Importantly, RRs of 20% to 22% are seen in second-line treatment. Work by a Swiss and Italian collaborative group has shown that the combination of docetaxel 85 mg/m2 with cisplatin 75 mg/m2 every 3 weeks is quite active, achieving an RR of 55% and median survival of 9 months. Hematotoxicity was the main adverse event but was manageable. In other respects the docetaxel/cisplatin doublet (TC) was relatively well tolerated. The same group demonstrated that continuous infusion of 5-fluorouracil (5-FU) 300 mg/m2 can be given on 2 weeks out of 3 to patients receiving TC. The addition of 5-FU, by this schedule, to TC (TCF) does not increase hematological toxicity, and does not compromise the tolerability of TC. An overall RR of 55% has been reported with TCF. A randomized phase II comparison of TC or TCF versus an ECF (epirubicin/cisplatin/5-FU) control arm is ongoing and should lead to a randomized phase III trial comparing TC or TCF with ECF. In an already completed international randomized phase II comparison of TC versus TCF (TAX-325), the three-drug combination proved significantly more active (RR 54% versus 32% with TC, among patients treated per protocol). Time to progression was also longer for TCF. Gastrointestinal (but not hematological) toxicity was less with TC. TCF was chosen for ongoing phase III comparison against a control 5-FU/cisplatin arm. It is possible that data from these randomized studies will confirm the value of docetaxel-based chemotherapy in advanced gastric cancer and that docetaxel combinations will also be effective in the multidisciplinary efforts to cure earlier stage cance

Synthesis and Antibacterial Activity of N,N-Diethyl-3-substituted-2-(4-methyl-phenylsulfonamido)alkanamides and their Arylsulfonamide Precursors

A series of N,N-diethyl-3-substituted-2-(4-methylphenylsulfon amido)alkanamides (8a-k) and their arylsulfonamide precursors (7a-k) have been synthesized via facile approach. The chemical structures of the synthesized compounds were confirmed by analytical data and spectroscopic means. The in vitro antibacterial screening of these compounds along with streptomycin, showed N,N-diethyl-2-(4-methylphenylsulfonamido) -3-phenylpropanamide (8j) to be the most active agent on Escherichia coli at MIC of 12.5 μg/mL and on Staphylococcus aureus at MIC of 25 μg/mL

Cu(II) and Fe(III) complexes of sulphadoxine mixed with pyramethamine: Synthesis, characterization, antimicrobial and toxicology study

Two new mixed ligands metal complexes of sulphadoxine and pyramethamine were prepared by using CuCl2.6H2O and FeCl3.6H2O. The complexes were characterized by elemental analysis, melting point determination, molar conductivity, metal content analysis (AAS), IR, magnetic susceptibility measurements and UV-Visible spectroscopy. Based on the analytical and spectroscopic data, the complexes were proposed to have the formulae [M1L1L2(Cl)2] and [M2L1L2(Cl)3] (where M1 = Cu(II), M2 = Fe(III)), L1 = sulphadoxine, L2 = pyramethamine). The spectroscopic data proposed L1 to be a monodentate ligand and coordinated through N atom of the NH2 group in both complexes. Also, L2 was proposed to be tridentate ligand and coordinated through N atom of the NH2 groups and through N atom of imine group. However, [M1L1L2(Cl)2] and [M2L1L2(Cl)3] were proposed to possess distorted octahedral geometry. Conductivity measurement values supported the non-electrolytic nature of the complexes. The complexes have been tested in vitro against a number of pathogenic bacteria [g(+) Escherichia coli, g(+) Proteus species, g(+) Pseudomonas aeruginosa and g(+) Salmonella typhi] by using disc diffusion method. Obtained results indicated that the metal complexes exhibited better antibacterial activities as compared to the ligands. Toxicology tests against some tissues of albino rat (Rattus novergicuss) revealed toxicity of the complexes in the kidney as compared to the parent drugs. [M1L1L2(Cl)2] was found to be toxic to the sera, livers and kidneys of the rats used, while [M2L1L2(Cl)3] was found to be non-toxic to the sera, livers and kidneys of the rats as their alkaline phosphatase (ALP) values showed non-significant difference to the control value

Synthesis, characterization, antimicrobial activity and toxicology study of some metal complexes of mixed antibiotics

Mixed ligand metal complexes of ampicillin and chloramphenicol prepared by using Ni(II), Co(II) and Fe(III) metal chloride hexahydrate were reported and characterized based on some physical properties and spectroscopic analysis such as AAS, UV, and IR spectroscopy. The complexes were proposed to have the formulae [ML1L2](Cl)n ( where M= Ni(II), Co(II), Fe(III); L1 = ampicillin, L2 = chloramphenicol, and n=2-3). IR spectra suggested that both L1 and L2 coordinated to the metal ions in a terdentate manner with �(O-H), �(C=O) and �(N-H) as donor sites in each of the ligands. From analytical and spectroscopic data obtained, the complexes were proposed to be of octahedral. The synthesized complexes, in compares to their ligands, were also screened for their antibacterial activity against isolated strains of Escherichia coli, Staphylococcus aureus and Klebsiella pneumonia by using agar diffusion method. The activity data showed the metal complexes to be more potent antibacterial than the parent drugs against the three bacteria species. However, toxicology tests against some tissues of albino rat (Rattus novergicuss) revealed toxicity of the complexes as compared to the parent drugs because the complexes were found to significantly increase (P<0.05) alkaline phosphatase from homogenates of liver and kidney tissues of the tested doses. However, there was no significant difference (P>0.05) in ALP of rat serum. The results generally indicated that more potent compounds with better physical properties and enhanced antimicrobial activities upon complexation have been prepared

Adenoviruses in Avian Hosts: Recent Discoveries Shed New Light on Adenovirus Diversity and Evolution

While adenoviruses cause infections in a wide range of vertebrates, members of the genus Atadenovirus, Siadenovirus, and Aviadenovirus predominantly infect avian hosts. Several recent studies on avian adenoviruses have encouraged us to re-visit previously proposed adenovirus evolutionary concepts. Complete genomes and partial DNA polymerase sequences of avian adenoviruses were extracted from NCBI and analysed using various software. Genomic analyses and constructed phylogenetic trees identified the atadenovirus origin from an Australian native passerine bird in contrast to the previously established reptilian origin. In addition, we demonstrated that the theories on higher AT content in atadenoviruses are no longer accurate and cannot be considered as a species demarcation criterion for the genus Atadenovirus. Phylogenetic reconstruction further emphasised the need to reconsider siadenovirus origin, and we recommend extended studies on avian adenoviruses in wild birds to provide finer evolutionary resolution

Facile Synthesis, Characterization and Antimicrobial Activity of 2-Alkanamino Benzimidazole Derivatives

Benzimidazole derivatives are known to represent a class of medicinally important compounds which are extensively used in drug design and catalysis. A series of 2-substituted benzimidazole derivatives 10a-i was herein synthesized from the reaction of o-phenylenediamine with some amino acids using ameliorable pathway. The chemical structures of the synthesized compounds were con rmed by IR, UV, 1H-NMR, 13C-NMR, Mass spectral and analytical data. The compounds were investigated for their antimicrobial activity alongside gentamicin clinical standard. The results showed that this skeletal framework exhibited marked potency as antimicrobial agents. The most active compound was 1H-benzo[d]imidazol-2-yl)methanamine, 10a

Comparative Study of Microwave-assisted and Conventional Synthesis of 3-[1-(s-phenylimino) Ethyl]-2H-chromen-2-ones and Selected Hydrazone Derivatives

In this study, 3-acetylcoumarin 1, used as the essential precursor was synthesized by the reaction of salicyaldehyde with ethyl acetoacetate in the presence of a catalytic amount of piperidine in solvent-free medium. Schiff bases 2-9 were obtained by the condensation reaction of 3-acetylcoumarin, 1 with various aniline derivatives while reaction of 3-hydrazinoquinoxalin-2-one with four different 6-susbtituted 3-acetylcoumarins afforded the corresponding hydrazones 10-13. Both Schiff bases and hydrazone products were synthesized under microwave irradiation method and conventional synthetic strategy for comparative study. The microwave assisted reaction was remarkably successful and gave both Schiff bases and hydrazones in higher yields at shorter reaction time compared to conventional heating method. The characterization of the synthesized compounds were structurally confirmed by analytical data as well as spectroscopic means which involved 1H-and 13C-nmr, ir, UV-visible and mass spectra

Comparative Study of the Antibacterial Activity of N, N-Diethylamido Substituted p-Toluenesulfonamides to their α-Toluenesulfonamide Counterparts

Reaction of p-toluenesulfonyl chloride with amino acids gave sulfonamides p-T1a-k which upon amidation afforded p-T2a-k. Similarly, treatment involving α-toluenesulfonyl chloride and amino acids afforded the sulfonamides α-T1a-k. These two classes of sulfonamides were synthetically modified at their COOH end position to achieve N,N-diethylamido substituted p-toluenesulfonamides p-T2a-k and α-toluenesulfonamides α-T2a-k, respectively. The chemical structures of the compounds were validated with IR, Mass spectra, NMR as well as elemental analytical data. Both classes of compounds were screened against Escherichia coli and Staphylococcus aureus and their activity were compared. It was remarkable to note that the α-toluene sulfonamides α-T2a-k were more active than their p-toluenesulfonamide counterparts p-T2a-k. Compound 1-(benzylsulfonyl)-N,Ndiethylpyrrolidine-2-carboxamide α-T2a was the most potent antibacterial compound on S. aureus with MIC value of 3.12 μg mLG1 while N,N-Diethyl-3- phenyl-2-(phenylmethylsulfonamide) propanamide α-T2j emerged as the best antibacterial motif against E. coli with MIC value of 12.5 μg mLG1. Hence, these compounds especially the α-toluenesulfonamide core structural templates are good candidates for further study for future drug discovery