ical data of all the synthesized compounds is shown in Table 1 . 3. Biological activity
All the synthesized 1,3,4-thiadiazolederivatives (6a–s) have been screened for both antibacterial and antifungal activities using cup-plate agar diffusion method by measuring zone of inhibition in mm. Eight different bacterial cultures S. aureus, Salmonella enterica, Vibrio cholera, Bacillus subtilis, Proteus mirabili, Escherichia coli V517, Mycobacterium smegmatics, Pseudomonas aeruginosa in nutrient agar medium, and one fungal culture Candida albicans in sabouraud’s dextrose agar medium ( Holla et al., 2002 ) were used. The results were com-
Following the discovery of 1, 3, 4-thiadiazole nucleus, numerous of structural modifications have been made to increase their biological activities. 1, 3, 4-thiadiazolederivatives display quite a broad spectrum of biological activities such as antimicrobial (1-3), anticonvulsant (4), antimycotic (5), anti-inflammatory (6), antiviral (7), antitubercular (8), analgesic (9). Several methods have been described for the synthesis of 1, 3, 4-thiadiazoles (10-11). Among these, the cyclization of thiosemicarbazide derivatives with different acids has reported to be a good strategy resulting in good yields. There are antimicrobial agents having different structures are frequently used in treatment of microbial infections. However, there is an increasing resistance to these drugs. Moreover, some of azole derivatives used as common antibiotics such as Amphotericin B posses a toxic effect on humans as well as their antimicrobial effects. To overcome the development of drug resistance, it is crucial to synthesize a new class of antimicrobials possessing different chemical properties from those of used commonly. In view of these facts, the aim of this present study is to synthesize and pursue the antimicrobial activity of the synthesized compounds containing 1, 3, 4-thiadiazolederivatives. The cyclization of 4-substituted phenyl thiosemicarbazides with different acid in presence of base gave the novel1, 3, 4-thiadiazoles.
The antibacterial screening was carried out in a laminar air flow unit and all types of precautions were strictly maintained to avoid any type of contamination during the test. Ultraviolet light was switched on for half an hour before working in the laminar hood to avoid any accidental contamination. Petri dishes and other glassware were sterilized in the autoclave at 121°C temperature and at a pressure of 15 lbs/sq inch for 15 minutes. Micropipette tips, culture media, cotton, forceps, blank disks, and so forth, were also sterilized. In disc diffusion method bacterial inoculum is prepared and inoculated into the entire surface of solid agar plate with a sterile cotton- tipped swab to form an even lawn. The paper disc 6mm in diameter impregnated with diluted test drug solution(500μg/ml in ethanol) was placed on the surface of each of agar plates using a sterile pair of forceps. The forceps were sterilized using flame. The plates were incubated for 2 - 3 days at 20 -25 0 C and
In view of synthesis of novel benzimidazoles; initially we have carried out the synthesis of 4-bromophenoxy aceticacid (2) by using 4-bromophenol and methylchloroacetate as a very simple starting materials. Then the condensation of 4- bromophenoxy aceticacid (2) with o-phenylenediamine (1) gives 2-(4-bromo-phenoxymethyl)-1H-benzimidaziole (3). N-alkylation, acylation and sulphonation of condensed product get series of some novel N-substituted 2-(4-bromo- phenoxymethyl)-1H-benzimidazole derivatives. We have synthesized compound 3 alternatively by using another method such as microwave irradiation. This gives scope for the alternate route to synthesize benzimidazoles in less reaction time. The structures of all the synthesized compounds were characterized by spectroscopic data.
The synthesis of the new compounds was carried out as outlined in Scheme 1. The starting compounds 2~amino~4~phenylthiazole (1) was prepared according to the literature method by refluxing acetophenone, thiourea and iodine. Then, 2~amino~4~phenylthiazole (1) was reacted with 3,4,5 trimethoxybezaldehyde (2) and mercaptoacetic acid (3) in presence of DCC to afford 2~(3, 4, 5~ trimethoxyphenyl)~3~(4~phenylthiazol~2~yl) thiazolidin~4~one (4). Further, reaction of 4 with various aryl aldehydes in presence of glacial aceticacid and sodium acetate under reflux condition gave corresponding 5~arylidine derivatives (5a-k). The structures of all the synthesised compounds were confirmed by the m.p., IR, 1 H~NMR and data
Synthesis of Novel4-Substituted Phenyl-(2-oxo-2H-chromen-3-yl) prop-2-en-1-ylidene Pyrimidine Derivatives To a mixture of substituted 3-acetyl coumarin (1), substituted benzaldehyde (2) and barbituric/thiobarbituric acid (3) in ethanol taken in a round bottom flask added 10 mol% of CAN and refluxed for about 5-6 h with constant stirring. The reaction was monitored by TLC. Reaction mixture was poured into the crushed ice and stirred for few minutes till the solid residue separated out, filtered, dried and recrystallized from ethanol.
Pyrazoles and their derivatives are important on account of use in therapy in different diseases 1-10 Antibacterial 11-15 , fungicidal 16-21 , antidiuretic 22-23 , anticancer 24-29 and anti-HIV 30-31 antitumour 32 , antianalgesic-inflamatory 33-37 , anticonvulsant 38-39 properties. Pyrazole and its derivatives normally do not occur in nature probably due to difficulty in constructing a N – N bond by living organism, the notable exceptions being 3-n-nonyllpyrazole 40 isolated from Hottuynia Cordate, α-amino-β-1-pyrazolylpropionic acid 41 isolated from water-melon seeds and the alkoloid Withasominie- 42 i.e., 4-phenyl-1, 5-trimethyenepyrazole (3) isolated from Withania Somnifera. The method for the synthesis of 2-(4'-formyl-3'-phenylpyrazole) 4-phenyl thiazole involving the condensation between acetophenone and 4-phenyl-2-hydrozino thiazole, which lead to the isolation of intermediate pyrazoline (Acetophenone hydrazone) in the presence of ethanol and glacial aceticacid. In continuation of our interest on the sysnthesis of novel hetrocyclic system during the present investigation we used vilsmeier-haack reaction on above intermediate pyrazoline, and gives few 2-(4'formyl-3'phenylpyrazole-1-yl) 4-phenylthiazole.
Into a 100 ml clean and dry round bottom flask containing 10 ml of glacial aceticacid, introduced thiazolidene-2,4-dione (0.02 mol, 2.34 gm) (1), appropriate benzaldehyde (0.02 mol) and sodium acetate (0.015 mol, 2.46 gm) was added, the reaction mixture was refluxed for 12 h . After completion of reaction, the mixture was allowed to cool to room temperature and the separated solid was filtered, washed with water and dried. The obtained benzylidene derivatives (2a-2g) were recrystallized from ethanol , the yield was 65-90 %.
acid which is converted into ethyl ester and subsequently synthesized the carbohydrazide 4. Thus obtained carbohydrazide was cyclized using phosphorous oxy chloride and thiosemicarbazide in order to get the key intermediate.This kind of novel ring systems not yet studied but few of the derivatives of pyridine containing 1, 3, 4-thiadiazolemoiety have been reported for their potent activity towards anticancer  anti-tubercular  anti- inflammatory[4, 5, 6] anti-bacterial [7, 8] and kinase inhibition[9, 10] properties. In this connection the author envisaged that by attaching 4-methoxy phenyl group at the second position of the pyridine and constructed 1, 3, 4-thiadiazole moiety.This constitutes the basic ring system and may enhance the Log-P values and thus increasing the potency. In order to validate this hypothesis the author has synthesized five novel amide derivatives of 1, 3, 4- thiadiazole [13, 14] compounds and tested their invitro cytotoxicity against cancer cell lines. The study revealed that the different 1, 3, 4-thiadiazolederivatives possesses excellent anticancer activity.In this synthesis compounds 6dhas showed good antiproliferative activity on HeLaand PANC-1 cell lines having IC50 of 4.6μM and 2.2μMrespectively.
A mixture of 1 (0.01 mol), aromatic aldehyde (0.01 mol) and anhydrous sodium acetate (0.01 M) in glacial aceticacid (25 ml) was refluxed for 5 h. After cooling it was poured on crushed ice and the resultant solid was washed with hot water and crystallized from 70% ethanol. TLC of the compounds was performed on silica gel-G using acetone: DMF (2:1) as solvent system. IR (KBr) cm -1 : 3450 (N-H),
Structure-activity relationships (SAR) are the traditional practices of medicinal chemistry, which try to modify the effect or the potency (i.e. activity) of bioactive chemical compounds by modifying their chemical structure. Medicinal chemists use the techniques of chemical synthesis to insert new chemical groups into the biomedical compound and test the modifications for their biological effects. The 5(2, 4- dihydroxy phenyl) 1, 3, 4, thiadiazole-2-amine’s set are well known compounds with interesting in vitro and in vivo anti-cancer profiles. On the basis of SAR we wish to report here with synthesis of eight novel 5-(2-fluoro and 2, 3-difluoro phenyl)-1, 3, 4-thiadiazole-2-amine and their derivatives.They are evaluated for anti-microbial activity They may have potential anti-cancer activity.
Adult Wistar rats of either sex with a body weight between 150-200g were used to study anti inflammatory activity. The animals were starved overnight. The test drug and standard were suspended in 1%CMC (control) and given orally. Thirty minutes later, 0.05 ml of 1% solution of carrageenan was given by a subcutaneous injection into the plantar side of the left hind paw of all the rats. The paw volume was measured by using plethysmometer after injection. Then the paw volume was again measured after 1h, 2h, 3h and 4h time intervals. The results were summarized in Table 1.
Non- steroidal anti-inflammatory drugs (NSAIDS) are still the most commonly prescribed drugs Worldwide for the treatment of inflammatory diseases like rheumatoid arthritis, osteoarthritis,orthopedic injuries, post operative pain and acute myalgias.Non-steroidal anti- inflammatory drugs (NSAIDs) are widely used to treat the sign and symptoms of inflammation,particularly arthritic pain. NSAIDs exert their anti-inflammatory effect mainly through inhibition of cyclooxygenases (COXs), the key enzyme in prostaglandin (PG) biosynthesis from arachidonic acid (AA). There are at least two COX isoforms COX-1 and COX-2. Constitutive COX-1 is responsible for providing cytoprotection in gastrointestinal (GI) tract whereas inducible COX-2 mediates inflammation. Traditional NSAIDs such as aspirin, diclofenac, flurbiprofen and ibuprofen are non-selective; however, they show greaterselectivity for COX-1 than COX-2. Therefore chronic use of NSAIDs may elicit appreciable GI irritation, bleeding and ulceration. The incidence of clinically significant GI side effects is high (over 30%) and causes some patients to abandon NSAID therapy. Thus the discovery of COX-2 provided the rationale for the development of drugs devoid of GI disorders while retaining clinical efficacy as anti-inflammatory agents. But the recent reports showed that selective COX-2 inhibitors (coxibs) could lead to adverse cardiovascular effects. Therefore, development of novel compounds having anti-inflammatory and analgesic activity with improved safety profile is still a necessity  .Hakan Bet al reported synthesis of series of some new 1, 2, 4 triazole derivatives as anti-microbial agents  . Mihaela Met alreported synthesis of some new 1, 3, 4thiadiazolederivatives as anti-inflammatory agents  .
Pyrazoles and its derivatives have been reported to possess significant antiarrhythmic and sedative (Bruno et al., 1990), hypoglycemic (Cottineau et al., 2002), antiviral (Baraldi et al., 1998), and pesticidal (Londershausen,1996) activities. Some of their derivatives have also been successfully tested for their antifungal (Chen & Li, 1998), antihistaminic (Mishra et al., 1998) and anti-inflammatory (Smith et al., 2001) properties.
mol%) followed by sodium ascorbate (10 mol%) and azide (0.45 mmol) was added. The reaction mixture was stirred for 1 h at room temperature, monitored by TLC. After complete conversion of starting materials the reaction mixture was diluted with water (25 mL), extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with brine (2×25 mL). The organic layer was dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The crude product was purified by column chromatography using 100-200 mesh silica gel and ethyl acetate in pet ether to afford corresponding 1,4-disubstituted 1,2,3-triazole analogues (6a-m).
This research article is aimed to synthesize and evaluate antimicrobial activity of a series of newly synthesized (5Z)-5-(E)-3-(1H-indoly-3- yl)-1-phenylallylideneamino)-2, 5-dihydro-1, 3, 4-thiadiazole-2-thiol 1(a-h). First of all N-substituted indole-3-carboxaldehyde derivatives are prepared from a mixture of Indole-3-carboxaldehyde (10 mmol), the appropriate alkylating reagent, anhydrous K 2 CO 3 and DMF was
A series of nine 1-(4-aryl-2-thiazolyl)-3,5-diaryl and six of 1-(4-aryl-2-oxazolyl)-3,5-diaryl-2- pyrazolin derivatives were prepared by reacting 3,5-diaryl-1-thiocarbamoyl-/or3,5-diaryl-1- carbamoyl- ∆ 2 -pyrazolines with substituted phenacyl bromide in ethanol. The structures of the synthesized derivatives were confirmed by IR, 1 H-NMR, 13 C-NMR as well as EIMS spectral data. Some of these derivatives were screened for their antimicrobial activity against Gram-positive, Gram- negative and pathogenic fungi, and showed a significant activity.
Despite significant progress in antimicrobial therapy, infectious diseases caused by bacteria and fungi remain a major health concern due to the development of resistance to existing antimicrobial drugs. The increasing incidence of bacterial resistance to large number of antibacterial agents such as glycopeptides, sulfonamides, β-lactams, nitroimidazoles, quinolones, tetracyclins, chloramphenicol and macrolides is becoming a major concern 1,2 . In
Agrobacterium and Erwinia sp.) and fungi (Candida albicans, Aspergillus flavus) under aseptic conditions. The medium for cultivation of the test organisms was nutrient agar, and the Petri-dishes were incubated at 30 °C for 24 hrs. The results were obtained by measuring the inhibition zones (in mm) caused by the various compounds on the microorganisms. From the results, it is obvious that most of the tested compounds posses slight or no activity at all towards the tested microorganisms. However, some compounds showed considerable activity against the tested bacteria such as 3, 4, and 5. Others exhibit moderate or slight activity against the fungi such as 6, 7.