Cytotoxicity of some 1-[2,4-dihydroxyphenyl]-3-[4-phenylpiperidin-1-yl] prop-2-en-1-one derivatives using MTT assay

Some N-substituted piperidine structures were synthesized and evaluated for cytotoxic activity against four different cell lines using the standard MTT assay method and Doxorubicin was used as the reference drug. The result of cytotoxic activity as a measurement of IC50 values revealed that three of the synthesized compounds were active against breast cancer cell line. Compound 6a bearing hydroxyl at para position of piperidine ring was the most active compound within this series. The N-subtituted piperidine with propene substructure could be considered as a lead structure for further studies of structure activity relationship to develop more potent compounds in future. The compounds were evaluated against four different cell lines using the standard MTT assay method and doxorubicin was used as the reference drug. The IC50 values were determined by constructing dose-response curves and revealed that three of the synthesized compounds were active against breast cancer cell lines. Compound 6a bearing hydroxyl at para position of piperidine ring was the most active compound within this series

Synthesis and biological investigation of some novel sulfonamide and amide derivatives containing coumarin moieties

New sulfonamide and amide derivatives containing coumarin moieties; oxo-2H-chromen-sulfamoylphenylacetamides and oxo-2H-chromen-arylacetamides were synthesized starting from diverse 2-chloroacetamide derivatives and a wide range of coumarins. The structures of the obtained compounds were elucidated by IR and NMR spectra and also analytical elemental analysis. In the next step, the above mentioned compounds were screened for their antimicrobial and antioxidant activities. Their antimicrobial activity was assigned using the conventional agar dilution method and the antioxidant activity was assessed using two methods, 1,1-diphenyl-2-picrylhydrazyl [DPPH] radical scavenging method and ferric reducing antioxidant power [FRAP] assay. Although the compounds showed no remarkable antimicrobial activities, most of them exhibited good antioxidant activities. Compounds 5b showed the most potent DPPH activity, whereas 8c was the most efficient compound in FRAP assay

Synthesis and investigation of antioxidant activities of 2-benzylidene-3-coumaranones

A number of 6-hydroxy-2-benzylidene-3-coumaranones were synthesized from condensation of 6-hydroxy-3-coumaranone with appropriate aldehydes and were evaluated for their antioxidant activities. The antioxidant activity was assessed using two methods, including, 1,1-biphenyl-2-picrylhydrazyl [DPPH] radical scavenging, and reducing power assays. Some of the benzylidene coumaranones showed antioxidant activity more than Trolox as reference antioxidant

Anti-Helicobacter pylori activity and structure-activity relationship study of 2-alkylthio-5-[nitroaryl]-1,3,4-thiadiazole derivatives

Nitro-containing heteroaromatic derivatives structurally related to nitroimidazole [Metronidazole] are being extensively evaluated against Helicobacter pylori isolates. On the other hand, 1,3,4-thiadiazole derivatives have also demonstrated promising antibacterial potential. In present study, we evaluated anti-H. pylori activity of novel hybrid molecules bearing nitroaryl and 1,3,4-thiadiazole moieties. Anti-H. pylori activity of novel 5-[5-nitroaryl]-1,3,4-thiadiazole derivatives bearing different bulky alkylthio side chains at C-2 position of thiadiazole ring, were assessed against three different metronidazole resistant H. pylori isolates by paper disk diffusion method. Most of the compounds demonstrated moderate to strong inhibitory response especially at 25 micro g/disk. The structure-activity relationship study of the compounds demonstrated that introduction of different alkylthio moieties at C-2 position of thiadiazole ring alter the inhibitory activity which is mainly dependent on the type of C-5 attached nitrohetercyclic ring. The promising compound of this scaffold, bearing 1-methyl-5-nitroimidazole moiety at C-5 and alpha -methylbenzylthio side chain at C-2 position of thiadiazole ring, showed strong inhibitory response against metronidazole resistant H. pyloriisolates at 12.5 micro g/disk [the inhibition zone diameter at all evaluated concentrations [12.5-100 micro g/disk] is > 50 mm]. Novel 5-[5-nitroaryl]-1,3,4-thiadiazole scaffold bearing different C-2 attached thio-pendant moieties with promising anti-H. pylori potential were identified. Among different nitroheterocycles, 5-nitrofuran and 5-nitroimidazole moieties were preferable for the substitution at C-5 position of 1,3,4-thiadiazole ring. Introduction of different alkylthio side chains at C-2 position of central ring alter the inhibitory activity which is mainly dependent on the type of C-5 attached nitrohetercyclic ring

Synthesis and antidiabetic evaluation of benzenesulfonamide derivatives

The complex metabolic syndrome, diabetes mellitus, is a major human health concern in the world and is estimated to affect 300 million people by the year 2025. Several drugs such as sulfonylureas and biguanides are presently available to reduce hyperglycemia in diabetes mellitus. These drugs have side effects and thus searching for a new class of compounds is essential to overcome this problems. A series of seven novel N-[4-phenylthiazol-2-yl]benzenesulfonamides derivatives were synthesized and assayed in-vivo to investigate their antidiabetic activities by streptozotocin-induced model in rat. These derivatives showed considerable biological efficacy when compared to glibenclamide, a potent and well-known antidiabetic agent, as a reference drug. Four of the compounds were effective, amongst which 13 show more prominent activity at 100 mg/Kg p.o. The experimental results are statistically significant at p < 0.05 level

2-Amino-4-[nitroalkyl]-4H-chromene-3-carbonitriles as new cytotoxic agents

A series of 2-amino-4-[nitroalkyl]-4/-chromene-3-carbonitriles were synthesized by an efficient multicomponent reaction in aqueous media using DBU as a catalyst at room temperature. Mild condition, environment friendly procedure and excellent yields are the main advantages of this procedure. The cytotoxic activity of target compounds were evaluated against three cancer cell lines MDA-MB-231, MCF-7 and T47D in comparison with etoposide as reference drug. Generally, all compounds showed good cell growth inhibitory activity with IC[50] values less than 30 microg/mL. Their activities were comparable or more potent than standard drug etoposide. The 6-bromo- derivatives 7e and 7f showed promising cytotoxic activity with IC[50] values in the range of 3.46-18.76 microg/mL, being more potent than etoposide against all tested cell lines

[Evaluation of Antifungal activity of new derivatives of Imidazole using Colorimetric method]

The incidence of invasive fungal infections has been increasing for two decades. A matter of concern in the treatment of fungal infections is the limited number of efficacious antifungal drugs. Many available drugs lead to the development of resistance, In order to seek new antifungal agents we assessed the antifungal activity of newly synthesized Imidazol compounds by a colorometric method. In this experimental study antifungal activity of the new Imidazol compounds against Candida albicans, Saccharomyces cervisiae, Aspergillus niger, Microsporum gypseom was investigated by colorometric method and results were compared to microdilution ones. 2-hydroxyphenacyl-azole and 2- hydroxyphenacyl-azolium compounds have been identified as a new class of azole antifungal agents with a good spectrum of activity. The colorimetric method is a simple microtiter method for determining the susceptibility of species of fungal against antifungal agents. Most derivatives showed significant in vitro antifungal activities against tested fungi with low MIC [minimum inhibitory concentration] values included in the range of 0.25-32 micro g/mL comparable to the reference drug Fluconazole

Comparison of the effect of non-antifungal and antifungal agents on Candida isolates from the gastrointestinal tract

Non-antifungal drugs appear promising in treatment of opportunistic infections of Candida spp. that are often resistant to current antifungals. The broth macrodilution method [NCCLS M27-P document] was used to compare the antifungal activity of trifluoperazine, pro-pranolol, and lansoprazole with that of ketoconazole and amphotericin B, using 50 yeast isolates from the Gl tract. The minimum fungicidal concentrations [MFCs], resistance rates and the time required for fungicidal activity of the drugs [2 - 48 hours] were determined. The most effective antifungal activity was exhibited by trifluoperazine. Its MFC was 32 microg/mL for Candida albicans [3.3% resistance] and Candida spp. [0% resistance] yeasts, and 64 ug/mL for Candida tropicalis with 10% resistance. The MFC for C. albicans and Candida spp. was comparable to that of ketoconazole. However, the time required for the inhibitory effect [6 hr] was shorter than that of ketoconazole [48 hr] or amphotericin B [24 hr]. The time required for the inhibitory activity on C. tropicalis was 24 hr, which was shorter than that of ketoconazole and amphotericin B [48 hr]. A considerable number [40%] of Candida spp. showed resistance to ketoconazole, and 20% of C. tropicalis showed resistance to amphotericin B. Trifluoperazine, an antipsychotic drug, exhibited effective antifungal activity with the MFC, comparable to ketoconazole [32 microg/mL]. Among the three yeast groups, C. tropicalis showed resistance to trifluoperazine and amphotericin B, and Candida spp. was considerably resistant to ketoconazole. Trifluoperazine could be considered as an alternative antifungal when encountering Candida spp. resistant to current antifungals

PEGylation of octreotide using an alpha,beta-unsaturated-beta-mono-sulfone functionalized Peg reagent

PEGylation is a well-established technique utilized to overcome the problems related to the therapeutic applications of pep tides and proteins. Reasons for the PEGylation of these biological macromolecules include reducing immunogenicity, proteolytic degradation and rapid clearance from blood circulation. Octreotide is an octapeptide analogue of naturally-occurred somatostatin. This peptide has elimination half-life of less than 2 h that requires frequent daily subcutaneous or intravenous administration. To address this issue, octreotide modification was investigated using bis-thiol alkylating PEG reagent. The required bisthiol alkylating reagent [V] was prepared from commercially available 4-acetyl benzoic acid in five steps. Octreotide disulfide bond was mildly reduced to liberate the two cysteine sulfur atoms followed by bis-alkylation to form PEGylated peptide. The PEG modification process was monitored through the reverse phase HPLC and 'H-NMR analysis. According to the HPLC chromatograms of PEGylation reaction, the peak with 30 min retention time was identified to be PEG-octreotide. In addition, H-NMR analysis showed a 7.44% degree of PEG substitution

Study of the anti-inflammatory and analgesic effects of novel rigid benzofuran-3, 4-dihydroxy chalcone by formalin, hot-plate and carrageenan tests in mice

It is reported that dihydroxy chalcones have analgesic and anti-inflammatory effects. Study of the structure activity relationship [SAR] shows that benzofuran-3-one derivatives may be more effective in this respect. In this study, a new [Z]-2-[3,4-dihydroxybenzylidene]-5-methoxybenzofuran-3[2H]-one [compound 5] was synthesized and its analgesic and anti-inflammatory effects were evaluated by formalin, carrageenan and hot-Plate methods in mice. The results showed that, compound 5 induced significant antinociceptive and anti-inflammatory effect [P< 0.01]. Maximum analgesia [42.6%] was obtained at dose of 25 mg/kg in the first phase of formalin test. The effect of compound 5 was higher [87.7%] in chronic phase of inflammation induced by formalin [P< 0.01]. Administration of 25 mg/kg of compound 5 inhibited the inflammation induced by carrageenan, 32.8% and 41.7%, 1 and 3 hour after carrageenan injection, respectively. In addition, this dose of compound 5, induces significant analgesia [20.2%] in hot plate test 45 minutes after injection [P<0.01]. Therefore it seems that compound 5 has potential for discovery of a compound with potent anti-inflammatory and analgesic effects and its scaffold could be use for further structural modifications

Quinolones: recent structural and clinical developments

Quinolones are a very important family of antibacterial agents that are widely prescribed for the treatment of infections in humans. Since their discovery in the early 1960s, the quinolone group of antibacterials has generated considerable clinical and scientific interest. Two major groups of compounds have been developed from the basic molecule: quinolones and naphthyridones. The 4-pyridone-3-carboxylic acid associated with a 5, 6-fused aromatic ring is the common chemical feature of bactericidal quinolones. In the resulting bicyclic ring, the 1-, 5-, 6-, 7-, and 8-positions are the major targets of chemical variation. Manipulations of the basic molecule, including replacing hydrogen with fluorine at position 6, substituting a cyclic amine residue at position 7 and adding new residues at position 1 of the quinolone ring, have led to improved breadth and potency of antibacterial activity and pharmacokinetics. One of the most significant developments has been the improved anti-Gram-positive activity of the newer compounds, such as moxifloxacin and garenoxacin. However, some of these structural changes have been found to correlate with specific adverse effects: the addition of fluorine or chlorine at position 8 being associated with photoreactivity, e.g. sparfloxacin; and the substitution of an amine or a methyl group at position 5 having a potential role in QTc prolongation, e.g. sparfloxacin and grepafloxacin. The clinical utility of this expanding class of antimicrobial agents, and the lower propensity for the development of resistance with the newer quinolones will need to be continually monitored in the changing therapeutic environment. Antibiotic drug choice will remain difficult in the presence of increasing resistance, but introduction of the new quinolones has created a new and exciting era in antimicrobial chemotherapy

Anti - pseudomona and anti - bacilli activity of some medicinal plants of Iran

The use of plants in treatment of burns, dermatophytes, and infectious diseases is common in traditional medicine of Iran. Based on ethno pharmacological and taxonomic information, antibacterial activities of methanol extracts of some medicinal plants of Iran were determined by In Vitro bioassays using agar diffusion-method against standard strains of Pseudomonas aeruginosa, P. fluorescens, Bacillus subtilis, B. cereus and B. pumilis at 20 mg/ml. From 180 plant species of 72 families, 78 species [43.3%] in 42 families [58.3%] showed antibacterial activities against B. cereus [88.4%], B. subtilis [39.7%], B. pumilis [37.1%], P. fluorescens [37.1%] and P. aeruginos [10.2%]. The most active plant families were Apiaceae, Compositae and Labiatae with 9, 8 and 7 active plant species respectively. Minimum inhibitory concentrations [MIC] of the active plants were determined using two fold serial dilutions. Most active plant against Bacilli was Myrtus communis L. with MIC of 1.87 mg/ml. For Pseudomonas species, Dianthus caryophyllus L. and Terminalia chebula [Gaertner] Retz. were more active with the MIC of 0.46 mg/ml for P. fluorescens and of 1.87 mg/ml for P. aeruginosa respectively