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The aim of this study was to design, synthesize, and investigate the in vivo anti-inß ammatory activity of some novel 2, 5-disubstituted -1, 3, 4-oxadiazole derivatives. Ethyl-4-acetamido phenoxy acetate (I) was prepared by the condensation of ethyl chloroacetate with starting material p-acetamidophenol in the presence of dry acetone and anhydrous potassium carbonate. Hydrazinolysis of (I) with hydrazine hydrate results in the formation of 4-acetamidophenoxy acetyl hydrazide (II), which on cyclisation with various substituted aromatic carboxylic acids in the presence of phosphorous oxychloride affords various 2, 5-disubstituted -1, 3, 4-oxadiazole derivatives (IIIa-IIIi). The newly synthesized compounds were characterized by IR, 1 HNMR, and MS spectral data. The titled compounds were screened for in vivo anti-inß ammatory activity using the carrageenan-induced paw edema method. A few of them manifested promising activity when compared with the standard drug Diclofenac sodium.

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Research on antitumor alkaloids isolated from plants have been actively explored in the last 30 years, in which the anti-tumor effects of the naturally occurring β-carboline derivative have been noticed recently after an intensive concentration on their high affinity to 5-HT [1] and benzodiazepines receptors [2,3] that cause CNS effect. As far the antitumor activity, harmine is a β-Carboline derivative shown to have strong cytotoxic activity to tumor cell lines in vitro. [4] It was recently discovered that β-carboline derivatives may function their antitumor activity through multiple mechanisms such as inhibiting topoisomerase-I and II, [5-9] β-kinase complex, [10,11] and intercalating DNA. [12] There are several reports on other biological activity of β-carboline derivatives [13,14] as well. QSAR is a useful tool for a retinal search of bioactive compounds. It provides a deeper insight into the mechanism of drug receptor interaction. Hence, in the present paper we report a QSAR study on a set of β-carboline derivatives for their in vitro antitumor activity against 6 different cell lines. In short, this study may provide a framework for designing a novel anti-tumor agent. MATERIALS AND METHODS Data set Data sets of 30 molecules have been taken from the published results. [12] The cytotoxic activity expressed as IC 50 values have been converted into-log molar concentration (p IC 50) to reduce the stewness of the data set. The structure and cytotoxic activity data (p IC 50) are given in Table 1. Molecular structure generation The structure of the β-carboline derivatives were sketched using ChemBioDraw Ultra 11.0 [15] and it has been saved as a template structure. The molecular mechanics (MM 2) method was applied to search for lower energy conformations for ABSTRACT A quantitative structure activity relationship (QSAR) study on β-Carboline derivatives as an anti-tumor agent was performed with 30 compounds of β-Carboline derivatives on different cancer cell lines from reported work. Molecular modeling studies were performed using ChemBioDraw Ultra 11.0. The sketched structures were subjected to energy minimization and the lowest energy structure was used to calculate the physiochemical properties. The regression analysis was carried out using a computer program called Valstat. The best models were selected from the various statistically signiÞ cant equations. From the derived QSAR model, it can be concluded that the cytotoxic activity of β-carboline derivatives is strongly inß uenced by the thermodynamic and electronic nature of the substituents.

A series of twenty molecules belonging to 2,5-disubstituted-1,3,4-oxadiazole derivatives of Diclofenac and Naproxen were designed, synthesized and their structures were confirmed by spectroscopy. The target compounds were evaluated for anti-inflammatory and analgesic activity. The result indicates that the compounds 12, 4, 6, 7 and 15 were found to have good analgesic and anti-inflammatory activities, while the compounds 12 and 14 were found to have good analgesic and the compound 22 were found to have good anti-inflammatory activities. HQSAR and Topomer QSAR studies were performed to get insights in the structures contributing for biological activity. The compounds bearing mono-substitution such as Cl, OCH3 and NO2 in the phenyl ring were found to have maximum analgesic and anti-inflammatory activities.