Several new pryrazolo-pyridazine derivatives (4a-h) were synthesized through multi-step synthesisand evaluated for their antimicrobialactivities. In the first step, 6-phenyl-2,3,4,5-tetrahydropyridazin-3-one (2) was prepared by reacting 4-(4-chlorophenyl)-4-oxobutanoic acid (1) with hydrazine hydrate. Then, aryl-aldehydes were reacted with 2 to furnish pyridazinone derivatives (3a-g). Finally, pyridazinones (3a-h) were reacted with hydrazine hydrate to furnish the title compounds (4a-h). The newly synthesized compounds were evaluated for their in vitro antibacterial and antifungal activities against six microbial strains. Compounds 4d, 4e and 4f exhibited significant antibacterial action, whereas compounds 4c and 4d showed potential antifungal activity. Compound 4d, 5-(4-Chlorophenyl)-3-(4-fluorophenyl)-3,3a,4,7-tetrahydro-2H-pyrazolo[3,4-c]pyridazine, emerged as lead compound having broad spectrum ofantimicrobial action.
The obtained data are presented in the Table I. The experiments indicated that all tested compounds 6a‒v showed more or less comparable activity with reference drug against all bacteria species with inhibition zone 20‒24 mm. Eight compounds (6a, 6b, 6e, 6k, 6l, 6m, 6r and 6q) exhibited good activity against different bacterial species, the activity of the rest was moderate. A very promising antimicrobial activity was shown by compounds 6k and 6l (Table I). Compound 6k is the most active against S. aureus, Sh. Dysenteriae Flexneri 6858 and E. coli showing inhibition zone almost equal to reference drug, while compound 6l was active only against S. aureus and E. coli. Compounds 6b, 6m and 6r also showed good activity against S. aureus with 23 mm inhibition zones. The same good activity possessed compound 6r against Sh.
The maintenance of ROS/RNS balance is carried out by endog- enous enzymatic antioxidant defenses such as superoxide dis- mutase, glutathione peroxidase, thioredoxin reductase and catalase and by non-enzymatic compounds such as glutathione, uric acid and coenzyme Q. If the internal production of antioxidants is not enough to neutralize all the ROS/RNS produced, a series of exoge- nous non-enzymatic antioxidants can be provided from human diet that includes carotenoids, phenolic compounds, and ﬂavonoids, among others . Thus, in the demand for new antioxidant agents, the design of novel and more effective scavengers of ROS and RNS is considered a key topic for several research groups. Continuing our interest in this area herein we report the synthesisof novel chro- mone and xanthone derivatives, as well as the scavenging activity of their hydroxyl constituents against ROS [superoxide radical (O 2 - ),
SYNTHESISAND EVALUATION OF ANTIMALARIAL ACTIVITY OF CURCUMIN DERIVATIVES. One of the main challenges in the development ofnew antimalarial drugs is to achieve a viable lead candidate with good pharmacokinetic properties. Curcumin has a broad range of biological activities, including antimalarial activity. Herein, we report the antimalarial activity of six curcumin derivatives (6–12) and an initial analysis of their pharmacokinetic properties. Five compounds have demonstrated potent activity against the P. falciparum in vitro (IC 50 values ranging from 1.7 to 15.2 µg mL −1 ), with moderate or low cytotoxicity against the HeLa
Quinones represent a wide and varied family of secondary metabolites of natural occurrence. The interest in these substances has been intensified in recent years due to their pharmacological importance and great structural variety. Many natural and syn- thetic quinone derivatives possess potent and varied pharmacolog- ical effects such as antitumor, 1–3 anti-inflammatory, 4,5 analgesic, 6
In the present study as in the part of medicinal chemistry programme, we have been synthesized a series ofnew sulfonamide derivatives, 9-(substitutedbenzenesulfonyl)-6-chloro-9H- purines and carbamate derivatives, 6-chloro-purine-9-carboxylicacid substituted alkyl/arylester by in situ fashion. Antimicrobial activity against three bacterial strains and three fungal strains at two different concentrations, 100 and 200 µg/mL including MIC values was investigated. Bio-screening data disclosed that all the title compounds exhibited promising antimicrobial activity at both the concentrations. Sulfonamide derivatives 7a, 7c and 7d, and one carbamate derivative 9a showed promising growth of inhibition of selected bacterial and fungal strains and these compounds showed MIC values in the range of 18.0- 25.0 µg/mL as compared with other title compounds and near activity of the standards. In whole comparison, the sulfonamide derivativesof 6-chloropurine are acted as potential antimicrobial agents than that of carbamate derivatives. The study of results encouraged us to design new library of purine derivatives as antimicrobial agents in future endeavors and might be worthy to medicinal chemistry.
acquired a special attention due to their wide range of therapeutic activities. Most derivatives are prepared by manipulation of pyridine and its simple homologues in a manner similar to chemistry of the benzenoid chemistry. However the simple pyridine compounds are prepared by the cyclization of aliphatic raw materials. The pyridine nucleus is found in a large number of commonly used drugs which have diverse pharmacological activities. Interests in the synthesisof multicyclic pyridine containing compounds have increased in recent years because of their biological and pharmacological activities. In our continuation work in the chemistry of pyridine nucleus, This inspired us to synthesize 6-Aryl-4-[4’-(p-chlorobenzyloxy)-3’- methoxyphenyl]-2-methoxy-3-cyanopyridines (1a-l) & 6-Aryl-4-[4’-(p-chlorobenzyloxy)-3’-methoxyphenyl]-2- ethoxy-3-cyanopyridine (2a-l) .
H. M. Ashour et al. 46 have synthesized a new series of thieno[20,30:4,5]pyrimido[1,2-b][1,2,4]triazines and thieno[2,3-d][1,2,4]triazolo[1,5-a] pyrimidines. The newly synthesized compounds were evaluated for their anti- inflammatory and analgesic activity using diclofenac Na as a reference standard. Additionally, the ulcerogenic effects and acute toxicity (ALD50) values of the active compounds were also determined. In general, the thieno[2,3-d][1,2,4]triazolo[1,5-a]pyrimidine derivatives exhibited better biological activities than the thieno[2 ’ ,3 ’
Abstract: We reported in this work the preparation of novel 1,4-disubstituted-1,2,3-triazoles derivatives from D- glucose and D-fructose and their in vitro antibacterial activity against Mycobacterium tuberculosis were evaluated. The chemical synthesis was performed based on the 1,3-dipolar cycloaddition reaction, andantimicrobial activity was determined based on Resazurin Microtiter Assay against Mycobacterium. None of the triazole glycoconjugates tested showed activity against these microorganisms.
ligand spectra showed bands at 3316-3304 and 1340-1348 cm –1 due to the stretching and deformation of the phenolic OH 16 . These are absent in the spectra of the complexes indicates the deprotonation of the hydroxyl group and co-ordination through oxygen. The band 1620-1628 cm -1 due to the azomethine group of the Schiff bases have shifted to lower frequency (1595-1605 cm -1 ) after complexation, indicating the bonding of nitrogen of the azomethine group to the metal ion and this can be explained by the donation of electrons from nitrogen to the empty d-orbital of the metal ion. The phenolic (C-O) stretching vibration that appeared at 1248-1255 cm -1 in Schiff bases shift towards higher frequencies (25-30 cm -1 ) in the complexes. This shift confirms the participation of oxygen in the C-O-M bond. The appearance of broad bands around at (3388-3420 cm -1 ) in the spectra of complexes may be due to water molecules. But this band is not presented in the Cu(II)-BSCA, indicating that the absence of water molecules in Cu(II) complexes. In the low frequency region, a band at 812 and 800 cm -1 in Co(II)-BSMA and Co(II)-BSCA (OH rocking), respectively, in the complexes, suggest the presence of coordinated water molecules in these complexes. Two new bands appearing in the low frequency range 538-556 cm -1 and 488-496 cm -1 are assigned to (M-O) and
A mixture of 4-piperidone hydrochloride monohydrate (1, 10 mmol) and various substituted aromatic aldehydes (20 mmol) in ethanol (10 mL) was stirred at room temperature (29 °C) for 10 min. The reaction mixture was cooled to 0 °C and conc. HCl (2.0 g, 20 mmol) was added dropwise. The resulting mixture was refluxed for about 4.5 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the crude product was filtered and recrystallized from ethanol to obtain pure 3a, 3b, 3d and 3f of this series in excel- lent yields. The compounds 3c and 3e were neutralized with 10 % NaOH (8 mL), extracted twice with chloroform (2×50 mL) and dried over by sodium sulphate. The combined organic layer was concentrated under reduced pressure and the crude product was purified by column chromatography using a 5 % mixture of methanol and chloroform as the eluent to obtain pure compounds 3c and 3e. Detailed structures for corresponding reactants and products are shown in Table I.
Research in this area is still very active and is directed towards the synthesisof compounds with enhanced pharmacological activity. Generally, these com- pounds are synthesized by the condensation of o-phenylenediamines with α , β -un- saturated carbonyl compounds, 5 β -haloketones or ketones. 6 A variety of re-
In order to ind an antimicrobial agent, nine compounds were synthesized and tested against Gram-positive, Gram- negative, and alcohol acid resistant bacteria and yeast. All compounds were active against all Gram-positive bacteria. One of the compounds was the most active, inhibiting Gram- positive, Gram-negative, and alcohol acid resistant bacteria and also the yeast. he other compounds had varied activity between classes of Gram-positive and acid alcohol resistant bacteria. Compounds containing chlorine in the molecule showed the best antibacterial activity, thus demonstrating the power of this atom on the bacteria. he compounds with sub- stituents nitro and methyl also showed signiicant activity. All the compounds presented the � coniguration. he chemical structures of the compounds were determined by physical methods IR, 1 HNMR, 13 CNMR and mass spectrometry.
new compounds were submitted to in vitro evaluation against pathogenic Gram-positive, Gram-negative bacteria and yeasts. The findings obtained showed that the compounds 2a, 2d, 2e and 2g were effective against some of the bacterial strains used, whereas the compounds 2d, 2e and 2i exhibited a moderate antifungal activity against the yeast strains evaluated. An initial structure activity relationship (SAR) was established.
All products were characterized by infrared (IR) and nuclear magnetic resonance (NMR) spectra. NMR was recorded on a Bruker Ultrashield 400 MHz device, using Tetramethylsilane (TMS) as the internal standard and Dimethylsulfoside-d 6 (DMSO-d 6 ) as a solvent. The chemical shifts are reported in ppm (δ), and coupling constant (J) values are given in hertz (Hz). Signal multiplicities are represented by s (singlet), d (doublet), t (triplet), c (quadruplet) and Figure 4. Reaction mechanism of quinoxaline 1,4-di-N-oxide on solid supports
The effect of synthesized compounds on the activity of c-Src kinase was determined by HTScan Src Kinase Assay Kit, catalogue number 7776 from Cell Signaling Technology (Danvers, MA, USA); according to manufacturer’s proto- col. Streptavidin-coated plates were purchased from Pierce (Rockford, IL, USA). In brief, the kinase reaction was started with the incubation of the 12.5 μL of the reaction cocktail (0.5 ng/μL of GST-Src kinase in 1.25 mM DTT) with 12.5 μL of prediluted compounds (dissolved in 1% DMSO) for 5 min at room temperature. ATP/substrate (25 μL, 20 μM/1.5 uM) cocktail was added to the mixture. The biotinylated substrate (catalogue number 1366) contains the residues surrounding tyrosine 160 (Tyr160) of signal transduction protein and has a sequence of EGIYDVP. The reaction mixture was incubated for 30 min at room temperature. The kinase reaction was stopped with the addition of 50 μL of 50 mM EDTA (pH 8.0). The reaction solution (25 μL) was transferred into 96-well streptavidin plates (Pierce, part number 15125), diluted with 75 μL double distilled water, and incubated at room temperature for 60 min. At the end of the incuba- tion, the wells were washed three times with 200 μL of 0.05% Tween-20 in PBS buffer (PBS/T). After that to each well was added 100 μL of phosphotyrosine antibody (P-Tyr-100) (1:1000 dilution in PBS/T with 1% BSA) and the wells were incubated for another 60 min. After washing three times with 0.05% Tween-20 in PBS/T, the wells were incubated with 100 μL secondary anti-mouse IgG antibody, which was HRP-conjugated (1:500 dilution in PBS/T with 1% BSA) for next 30 min at room temperature. The wells were washed five times with 0.05% Tween-20 in PBS and then were incubated with 100 μL of 3,3',5,5'-tetramethylbenzidine dihydrochloride (TMB) sub- strate for 5 min. The reaction was stopped by adding 100 μL/well of stop solution to each well and mixed well and read the absorbance at 450 nm using a microplate reader (Molecular devices, spectra Max M2). IC 50 values of the
decoration in Airtam "the sculpture with the busts of musicians, gift-bearers was subjected to the unified principle of division of the entire space into rhythmic segments" [47, 86].As an example, one may consider the case when the sculpture had a religious or symbolic significance, and was a crucial element in resolving the entire interior ("Hall of Warriors" in Toprak-kale). But on the whole, in contrast to a more constrained medieval sculpture, antique one differed in realistic nature (right arrangement of the figures), expressiveness (the types of faces and their emotions), naturalness (in different curves of the body), through which the aesthetic sides of the structures were emphasized. Monumental characters of the structures, their ideological concepts (for example, the idea of greatness) were emphasized by means of sculpture. And, the most important aspect, the sculpture differed in architectonic manner (Buddhas - under the arches, gandharvas– between the acanthuses), as the determinant factor was still the scale of the monument, the height of the walls, the conditions of observation, the very architectonics of the interior. A high quality performance, especially in the Greco-Bactrian period, testified to the high skills of the artists, in the best traditions of Hellenic arts. "The artist could be acourt master from Seleucid accompanying the king to a distant Bactria" [30, 190]. It is assumed that in Bactria existed at least three sculptural schools; their students were familiar with Asia Minor sculpture schools [48, 125p]. Smooth walls of buildings were divided not only horizontally –by friezes, zofors, but also vertically - through door and window openings, columns and pilasters. The synthesisof architecture and decorative plastic forms, generally typical for later Hellenistic states, could be seen in the ancient Bactrian capitals - Corinthian and composite ones, representing a complete architectural form. Professional masters "were widely using the approach of architectonic
JEOL 500 MHz spectrometers at ambient temperature using tetramethylsilane as an internal reference. Mass spectra were recorded on a JEOL JMS AX-500 spectrometer by using electron impact ionization at 70 eV. Elemental analyses were carried out by the University of Cairo Microanalytical Laboratories. The antimicrobial tests were carried out at the Pharmaceutical Department, Faculty of Pharmacy, Alexandria University. ChemDraw-Ultra-11.0 has been used for the nomenclature of the prepared compounds.
During the survey of brachyuran fauna of Matuta planipes (Fabricius, 1798) has four adult female and two male species were collected in Chennai coast using trawl net. Trawl net hauled from depth of 40 m to 60 m. The specimen was preserved in 10% formalin and its taxonomy was confirmed to species level using various literatures (Sethuramalingam and Ajmalkhan, 1991; Jayabaskaran et al., 2000). The specimen was deposited in the Department of Zoology, Sir Theagaraya College, Chennai, Tamil Nadu, India.
Parasitic diseases are the cause of much suffering and death throughout the world, mainly in underde- veloped areas like Africa, Asia and Latin America. In these regions, the economic and social impacts caused by these sicknesses are very high because the parasites infect millions of people. Among these parasites, the Protozoa genera are responsible for the principal sick- nesses, and leishmaniasis is one of the strictest para- sitic diseases caused by multiple species of Leishmania (WHO 2008). The disease is endemic in tropical regions, affecting over 12 million people in 88 countries and its clinical manifestations can occur in cutaneous, muco- cutaneous and visceral forms (Croft & Yeardley 2002, Murray et al. 2005). The main health organisations are concerned about these statistics due to the significant number of cases (Nwaka & Hudson 2006). Despite this, the therapies currently available to treat this illness are deficient and outdated and most present several side- effects. Moreover, the widespread development of resist- ance by certain strains of leishmaniasis to antimonial compounds contributes to poor health conditions in un- derdeveloped countries. Chemotherapy of leishmaniasis (Croft & Yeardley 2002, Nwaka & Hudson 2006) con- sists of using intravenous drugs like antimonial com- pounds as first-choice drugs and amphotericine B as second-choice. In countries where many resistance cases to the antimonial drugs are reported, this antibiotic is