Novel quinazolinone derivatives: synthesis and antimicrobial activity

4-(4-Oxo-4H-3,1-benzoxazin-2-yl)phenyl-4-methylbenzenesulfonate (2) was prepared and reacted with some primary aromatic amines, e.g., aniline, p-chloro aniline, p-methoxy aniline, p-amino benzoic acid and p-amino acetophenone. It reacted also with some heterocyclic amines, e.g., 2-aminothiazole, 2-aminobenzothiazole, 5-amino-4-phenylazo-2,4-dihydropyrazol-3-one and 3-amino-2-methylquinazolinone and with diamines; e.g., o-phenylenediamine, p-phenylenediamine, ethylenediamine, semicarbazide hydrochloride and thiosemicarbazide under different conditions. On the other hand, compound (2) reacted with both sodium azide and active methylene compounds, e.g., ethylcyanoacetate and ethylacetoacetate to give (19) and (20), respectively. All new prepared compounds were subjected to antimicrobial activity evaluation.     

Design, synthesis of some 2,6,9-trisubstituted purinyl thioureido derivatives and evaluation of antimicrobial activity

Some new trisubstituted purinyl thioureido were synthesized and evaluated for their in vitro antimicrobial activity against Gram positive and Gram negative strains and antifungal strain using a micro dilution procedure. Synthesized compounds 6a–j prove to be effective with minimum inhibitory concentration (MIC) (mg?ml^?1), among them 6a, 6d, and 6e showed excellent activity against a panel of microorganisms. The newly synthesized compounds were characterized using IR, ¹H-NMR, and elemental analysis.     

Synthesis and antimicrobial activity evaluation of some new adamantane derivatives

In this study, some new Schiff bases were synthesized as antimicrobial agents using benzaldehyde derivatives and 1- or 2-aminoadamantane. The structures of the synthesized compounds were confirmed by IR, 1H-NMR and elementary analysis. Antimicrobial activities of the synthesized compounds were tested against some bacteria and yeast-like fungi. The antimicrobial activity of the compounds was investigated by broth microdilution method using two Gram positive (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212) and two Gram negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853) bacteria and yeast-like fungi (Candida albicans ATCC 90028, Candida krusei ATCC 6258, Candida parapsilosis ATCC 22019). The antifungal activity of 1-((2-chloro-3,4-dimethoxybenzylidene) amino(adamantane (compound 3) against C. krusei and C. parapsilosis (minimal inhibitory concentration 32 micrograms/ml) was higher than that of the other tested compounds.     

A facile route for the synthesis 1,4-disubstituted tetrazolone derivatives and evaluation of their antimicrobial activity

A facile route for the synthesis of 20 new 1,4-disubstituted tetrazolone derivatives from allyl bromides of Baylis–Hillman adducts and various 1-substituted tetrazolones is described. All the synthesized compounds were screened for in vitro antibacterial and antifungal activity. Out of 20 newly synthesized compounds 16 compounds showed very good activity against the Gram-positive bacteria Bacillus subtilis compare to the standard drug ciprofloxacin. The compounds 7b, 7n and 7o showed remarkable activity against both the Gram-positive bacteria B. subtilis and Staphylococcus aureus. Two compounds 7l and 7o showed very good activity against the Gram-negative bacteria Escherichia coli. The compounds, when tested for antifungal activity four compounds— 7b, 7l, 7o and 7s— showed very good activity against the strain Aspergillus niger, whereas seven compounds— 7e, 7g, 7h, 7l, 7o and 7s— display good activity against Candida albicans. Compounds 7b, 7e, 7g, 7l and 7o exhibited very good-to-high activity towards all the strains tested.     

Microwave-assisted synthesis of novel 1,2,3-triazole derivatives and their antimicrobial activity

An environmentally benign and economic synthesis of 1-[7-(1-benzyl-1H-[1,2,3]triazol-4-ylmethoxy)-2,2-dimethyl-chroman-6-yl]-3-aryl-2-propen-1-ones and 1-[5-(1-benzyl-1H-[1,2,3]triazol-4-ylmethoxy)-2,2-dimethyl-chroman-6-yl]-3-aryl-propen-1-ones is described. The procedure takes place by the 1,3-dipolar cycloaddition (‘‘click-reaction’’) between azides and alkynes catalysed by copper (I) salts. The simplicity of this reaction and the ease of formation and purification of the resulting products have opened new opportunities in generating vast arrays of compounds with biological potential. The structures of the synthesized compounds have been established on the basis of physical and spectral data. All the synthesized compounds were tested in vitro for their antibacterial and antifungal activities. Compounds 8a (R₁=H, R₂=H, R₃=H), 8b (R₁=H, R₂=CH₃, R₃=H), 8d (R₁=OCH₃, R₂=OCH₃, R₃=H), 8e (R₁=OCH₃, R₂=OCH₃, R₃=OCH₃), 13a (R₁=H, R₂=H, R₃=H), 13d (R₁=OCH₃, R₂=OCH₃, R₃=H) and 13e (R₁=OCH₃, R₂=OCH₃, R₃=OCH₃) showed significant antimicrobial properties.     

Isonicotinic acid hydrazide derivatives: synthesis, antimicrobial activity, and QSAR studies

A series of isonicotinic acid hydrazide derivatives (1–19) was synthesized and tested in vitro for antimycobacterial activity against Mycobacterium tuberculosis and antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Candida albicans, and Aspergillus niger and the results indicated that the compounds with OH, SCH₃, and OCH₃ groups were found to be active against the tested strains. None of the test compounds were active against a broad variety of RNA and DNA viruses at subtoxic concentrations, except 8, that showed some selective anti-reovirus-1 activity. The multi-target QSAR models were found to be effective in predicting the antimicrobial activity of the isoniazid derivatives and indicated the importance of nuclear repulsion energy (Nu.E) in explaining the antimicrobial activity of isoniazid derivatives. The developed QSAR models were validated using the external test set of synthesized derivatives.     

Lasiokaurin derivatives: synthesis,antimicrobial and antitumor biological evaluation,and apoptosis-inducing effects

Herein, a series of lasiokaurin derivatives were designed and synthesized. All the derivatives together with lasiokaurin and oridonin were tested for their antimicrobial and antiproliferative activity. Compound 16 showed the most promising antimicrobial activity with MICs of 2.0 and 1.0 μg/mL against Gram-Positive bacteria S. aureus and B. subtilis, respectively. All the synthetic lasiokaurin derivatives showed better antiproliferative activity than parent compound lasiokaurin 1. Compound 10 exhibited the strongest cytotoxicity with IC₅₀ values of 0.47 and 0.20 μM against MGC-803 and CaEs-17 cells, accordingly. Moreover, it was shown to have potent antitumor activity in vivo in a murine model of MGC-803 gastric cancer. Preliminary SARs were also concluded based on obtained data. The apoptosis-inducing effects of 10 were further investigated using CaEs-17 cells. The results showed that lasiokaurin derivative 10 could induce apoptosis via mitochondria related pathway and arrest CaEs-17 cell cycle at S phase. Compound 10 could also affect apoptosis-related proteins that was up-regulation of CDK2 and down-regulation of ATM and cyclin A1.     

Soft antimicrobial agents: synthesis and activity of labile environmentally friendly long chain quaternary ammonium compounds

A series of soft quaternary ammonium antimicrobial agents, which are analogues to currently used quaternary ammonium preservatives such as cetyl pyridinium chloride and benzalkonium chloride, were synthesized. These soft analogues consist of long alkyl chain connected to a polar headgroup via chemically labile spacer group. They are characterized by facile nonenzymatic and enzymatic degradation to form their original nontoxic building blocks. However, their chemical stability has to be adequate in order for them to have antimicrobial effects. Stability studies and antibacterial and antiviral activity measurements revealed relationship between activity, lipophilicity, and stability. Their minimum inhibitory concentration (MIC) was as low as 1 microg/mL, and their viral reduction was in some cases greater than 6.7 log. The structure-activity studies demonstrate that the bioactive compounds (i.e., MIC for Gram-positive bacteria of <10 microg/mL) have an alkyl chain length between 12 and 18 carbon atoms, with a polar headgroup preferably of a small quaternary ammonium group, and their acquired inactivation half-life must be greater than 3 h at 60 degrees C.     

Quaternary ammonium derivatives as spasmolytics for irritable bowel syndrome

Quaternary ammonium derivatives such as cimetropium, n-butyl scopolammonium, otilonium and pinaverium bromide have been discovered and developed as potent spasmolytics of the gastrointestinal tract. Their pharmacological activity has been proven in both "in vivo" and "in vitro" studies of hypermotility. "In vitro" experiments showed that they possess antimuscarinic activity at nM level but only pinaverium and otilonium are endowed with calcium channel blocker properties. These latter compounds relaxed the gastrointestinal smooth muscle mainly through a specific inhibition of calcium ion influx through L-type voltage operated calcium channels. Molecular pharmacology trials have indicated that pinaverium and otilonium can bind specific subunits of the calcium channel in the external surface of the plasma membrane and in this way they block the machinery of the contraction. Recent evidence showed that otilonium is able to bind tachykinin NK(2) receptors and not only inhibits one of the major contractile agents but can reduce the activation of afferent nerves devoted to the passage of sensory signals from the periphery to the central nervous system. Thanks to their typical physico-chemical characteristics, they are poorly absorbed by the systemic circulation and generally remain in the gastrointestinal tract where they exert the muscle relaxant activity by a local activity. Some differences exists in the absorption among these compounds: both n-butyl scopolammonium and cimetropium are partially taken up in the bloodstream, pinaverium has a low absorption (8-10 %) but is endowed with an excellent hepato-biliary excretion and otilonium, which has the lowest absorption (3 %), is almost totally excreted by faeces. Quaternary ammonium derivatives are widely used for the treatment of irritable bowel syndrome and recent meta-analyses have supported their efficacy in this disease. Due to its therapeutic index, the use of n-butyl scopolammonium is more indicated to treat acute colics than a chronic disease such as irritable bowel syndrome. Taking into consideration the published trials carried out with validated methodology in irritable bowel syndrome, cimetropium and otilonium are the best demonstrated drugs for the improvement in global assessment, pain and abdominal distension.     

Design, synthesis and antimicrobial evaluation of novel 2-aryl-thiazolidin-4-one derivatives

ABSTRACT: Novel 2-arylthiazolidin-4-one derivatives (8a-q and 11) have been synthesized in good-to-excellent yields (70-96%) by one-pot three-component condensation-cyclization reaction of aromatic or aliphatic primary amines, aromatic aldehydes, and thioglycolic acid in polypropylene glycol at 110°C temperature. The in vitro antimicrobial activity of the synthesized 2-arylthiazolidin-4-ones was investigated against a panel of six pathogenic fungal strains, a Gram-positive and three Gram-negative bacteria. Results revealed that the compounds (8a-d) bearing 3-(4-(1H-imidazolylmethyl)phenyl)-substituent displayed significant antibacterial efficacy specifically against Klebsiella pneumoniae (minimum inhibitory concentration 12.5 μg/mL). In addition, some of the synthesized compounds have also shown antimicotic activity against Sporothrix schenckii, Trichophyton mentagrophytes, and Aspergillus fumigatus at the concentration of 50 μg/mL.     

苯丙烯酰胺类化合物的设计、合成及抗HBV活性评价

目的合成苯丙烯酰胺类化合物并考察其抗HBV活性。方法以甘氨酸为起始原料,经过与4-硝基苯甲酰氯缩合,再与2-甲氧基苯甲醛环合,所得产物与氨基醇类化合物反应得到目标化合物。采用MTT法评价目标化合物的细胞毒性,实时荧光定量PCR检测细胞中HBV DNA复制程度,分别计算抑制率、IC_(50)及SI。结果制备了6个苯丙烯酰胺类化合物。化合物5a(IC_(50):2.06μmol·L~(-1),SI:26.35)、5b(IC_(50):0.95μmol·L~(-1),SI:69.58)和5c(IC_(50):4.36μmol·L~(-1),SI:19.86)对HBV DNA复制的抑制活性显著好于先导物MTS(IC_(50):12.57μmol·L~(-1),SI>7.96),对HepG2耐药细胞的HBV DNA也具有较强的抑制作用。结论化合物5a~5c具有进一步研究的价值。     

5-phenyl-1-benzofuran-2-yl derivatives: synthesis, antimicrobial, and antioxidant activity

Previously unknown biphenyl containing 5-phenyl-1-benzofuran-2-yl derivatives; methanones (2a–i), tertiary alcohols (3a–l), and carbinols (4a–f) were synthesized and evaluated for their antimicrobial and antioxidant activities to study the effect of functionalization at the carbonyl carbon and substitution at biphenyl ring on these activities. The introduction of hydroxyl group at carbonyl carbon enhanced the antioxidant property (3a, 3g, 3h, 4a, and 4b), while antimicrobial activity decreased; the carbinol and tertiary alcohols corresponding to methanone 2a and 2b showed no antimicrobial activity. Biphenyl methanones 1, 2a, 2f, and 2g exhibited antimicrobial activity with minimal inhibitory concentration ranging between 0.001 and 0.500 mg/mL, tertiary alcohols 3a, 3g, and 3h and carbinols 4a and 4b exhibited the promising antioxidant property. The mode of action of these active compounds was carried out by docking of receptor GlcN6P synthase with newly synthesized candidate ligands 1, 2a, 2e, 2f, 2g, 2h, 3a, 3g, 3h, 4c, and 4d.     

Design, synthesis, and evaluation of thiazolidinone derivatives as antimicrobial and anti-viral agents

A series of 1,3-thiazolidin-4-one derivatives were prepared by the reaction of respective aromatic amine, aromatic aldehyde, and thioglycolic acid in dry benzene/toluene. The newly synthesized compounds were characterized on the basis of elemental analysis, IR, (1) HNMR, and mass spectra. The newly synthesized final compounds were evaluated for their in vitro antibacterial, antifungal, and anti-viral activities. Preliminary results indicated that some of the compounds demonstrated antibacterial activity in the range of 7-13 μg/mL, antifungal activity in the range of 13-17 μg/mL, comparable with the standard drugs, ciprofloxacin and fluconazole. Structure-activity relationship studies revealed that the nature of the substituents at the 2 and 3 positions of the thiazolidinone nucleus had a significant impact on the in vitro antimicrobial and anti-viral activity of these classes of agents.     

1,2,3,4,-Tetrahydro-1,2-diazepine derivatives: synthesis and evaluation of antileukemic activity

A series of 3-aryl or etheroaryl-6-cyano-7-phenyl-1,2,3,4-tetrahydro-1,2-diazepin- 5-ones was synthesized and evaluated for its antitumor activity against P388 leukemic tumor system in mice. None of the tested compounds showed significant antitumor properties.     

1,8-naphthyridine derivatives: synthesis and pharmacological evaluation of beta-receptor blocking activity.

The synthesis of a number of 1-alkyl-7-(2-hydroxy-3-alkylaminopropoxy)-1,8-naphthyridin-2-ones is described. The compounds studied were prepared by reaction of 1-alkyl-7-hydroxy-1,8-naphthyridin-2-ones with epichlorohydrin. The substituted epoxy intermediates obtained were allowed to react with amines and gave the desired products. All the compunds prepared were devoid of beta-blocking activity.