Structure-activity relationship: As regards the relationships between the structure of the heterocyclic scaffold and the detected antibacterial

properties, it seems that there is no difference. Probably in this case the nature of the heterocyclic ring is not so important for antimicrobial activity. Moreover, the presence of substituents in different positions of both thiazole and benzothiazole moieties causes a certain change of activity. Among benzothiazoles, 4-amino- and 4-nitrosulfonamides having a halogen as substituent (compounds 7, 12 and 13) or carrying an ethoxy group (compounds 8 and 11) exhibit inhibitory properties lower than those of the corresponding methyl substituted ones (compounds 6 and 10, respectively). On the other hand, for the latter compound a decreased activity towards Bacillus subtilis and an enhancing inhibition of Staphylococcus aureus can be detected, when compared with unsubstituted compound 9. As concerns thiazole derivatives, the introduction in compound 2 of a lipophilic methyl group (compound 3) abolishes the activity against Bacillus subtilis, while the presence of a bulky group (-CH ) in compound 4 does enhance its inhibition properties. From the obtained results it is clear that the major role for antibacterial activity is played by the substituent in the 4-position of the aromatic ring of sulfonamides. It is evident that sulfonamides with an amino group in the C-4 position of the phenyl ring are the most active compounds. Thus, the replacement of the amino group with nitro leads to a dramatic decrease in

The solvent was removed under reduced pressure and the residue obtained was triturated with water. The solid precipitate thus obtained

Motif

Lipoxygenases constitute a family of non-haem iron containing dioxygenases that are widely distributed in animals and plants. These are involved in arachidonic acid metabolism, generating various biologically active lipids that play important roles in inflammation. Thrombosis and tumor angiogenesis, the formation of new capillary vessels from preexisting ones, underpins a number of physiological processes and participates in the development of several pathological conditions such as arthritis and cancer. Lipoxygenases are, therefore, potential targets for rational drug design and discovery of mechanism-based inhibitors for the treatment of a variety of disorders such as bronchial asthma, inflammation, cancer, and autoimmune diseases. In Vitro Lipoxygenase Inhibition Assay.

Lipoxygenase-inhibiting activity was conveniently measured by slightly modifying the spectrometric method developed by A. L. Tappel. Lipoxygenase (1.13.11.12) type I-B and linoleic acid were purchased from Sigma (St. Louis, MO). All other chemicals were of analytical grade. The reaction mixture contained 160 L (100 nM) of sodium phosphate buffer (pH 8.0), 10 Lof test compound solution, and 20 L of lipoxygenase solution and was incubated for 10 min at 25 C. The reaction was then initiated by the addition of 10 L of linoleic acid (substrate) solution, with the formation of (9Z,11E)(13S)-13-hydroperoxyoctadeca-9,11-dienoate. The change of absorbance at 234 nm was followed for 6 min. Test compounds and the control were dissolved in methanol. All the reactions were performed in triplicate in a 96-well microplate in a SpectraMax 340 (Molecular Devices). The IC50 values were then calculated using the EZ-Fit Enzyme kinetics program (Perrella Scientific Inc., Amherst). The percentage (%) inhibition was calculated as (E - S)/E 100, where E is the activity of the enzyme without test compound and S is the activity of enzyme with test compound.

Emergence of resistant bacterial and fungal strains towards existing antimicrobial agents is one of the major motives for research and development of new molecules to defend them. Substituted 1,3,4-oxadiazoles are of considerable pharmaceutical and material interest, which is documented by a steadily increasing number of publications and patents.1,3,4-oxadiazoles show various biological activities and have been synthesized from different compounds. Research on 1,3,4-oxadiazole and their synthetic analogs have revealed a variety of pharmacological activities including antimicrobial, anti-tubercular and insecticidal agents. Some of these compounds have also analgesic ,anti-inflammatory, anti-cancer, anti-HIV agent, anti-Parkinson and anti-proliferate agent, It was our interested to make novel derivatives of the titled compounds and evaluate the anti-bacterial, analgesic, antiinflammatory and anti tubercular activities. A series of 2, 5-disubstituted 1,3,4-oxadiazoles were prepared which contain pyridine and piperidine ring .The structure of synthesized compounds has been characterized by spectroscopic data and elemental analysis. All the compounds have been screened for their antimicrobial activity. 1,3,4-oxadiazoles belong to the group of heterocyclic compounds that have been attracting attention for last two decades due to their wide range of biological interactions. Many of them exhibit antibacterial, anticonvulsant, anticancer activities and are used to fight infections involving AIDS. 2,5-disubstituted-1,3,4-oxadiazoles have been reported as remarkable antidepressive, anticonvulsive, antiinflamatory, antimicrobial, antimitotic, anelgesic, hypoglycemic, antifungal, muscle relaxant, ransquilising agents as well as herbicidal, insecticides. Due to the interesting activity of 2, 5-disubstituted 1,3,4-oxadiazole as biological agents considerable attention has been focused on this class. The pharmaceutical importance of these compounds lies in the fact that they can be effectively utilizing as antibacterial, anti tubercular and insecticidal agents. Some of these compounds have also analgesic, anti inflammatory, anticancer, anti-HIV agent, antiParkinson and anti-proliferate agent. In addition, 1,3,4-oxadiazole have played a crucial part in the development of theory in heterocyclic chemistry and also used extensively in organic synthesis.

Among the methods employed in synthesis of 1,3,4-oxadiazole, condensation of hydrazide and its derivatives with variety of substituted acids and bases are commonly used. 2,5disubstituted 1,3,4-oxadiazole can be conveniently synthesized by the treatment of pyridine-4-carbohydrazide with different acids and bases and carbon disulfide in basic and acidic media. Therefore, as a part of our program focused on 1,3,4-oxadiazole with biological activity, and in connection with our interest in the chemistry of 2,5-disubstituted 1,3,4-oxadiazole. In this paper we report the synthesis of some novel 2,5-disubstituted 1,3,4oxadiazoles and its antibacterial activity. It was probable that the 1,3,4-oxadiazole ring 2,5-disubstituted with the potential drug molecules containing pyridine, piperidine and indole rings will enhance the activity of the molecule. This paper reports the synthesis and biological screening of some new 2,5disubstituted 1,3,4-oxadiazoles using standard procedure with slight modification. Search for novel medicinally active compounds and optimization of fast and efficient approaches to synthesize them with desired function has drawn considerable attention in recent years.