Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (v.14, #2)

Meet Our Associate Editors by Joseph V. Pergolizzi, Marie-Aleth Lacaille-Dubois (79-80).

An update on Anti-inflammatory Compounds: A Review by Ashwani Kumar Dhingra, Bhawna Chopra, Rameshwar Dass, Sanjeev Kumar Mittal (81-97).
Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process. Also, it has been reported to be associated with the onset of various cancers. An effective anti-inflammatory drug should be able to inhibit the development of inflammation without interfering in normal homeostasis. Current approaches to overcome the inflammation include the use of immune selective anti-inflammatory derivatives, selective glucocorticoid receptor agonist, resolvins and protectins and TNF inhibitors. A number of herbal drugs have been identified in the past that can target inflammatory cytokines. This review mainly focuses on the newer molecules to combat the inflammation and also emphasise on various studies carried out in the past. Thus, the high prevalence of inflammation obliges the development of new drugs; therefore, a safe and efficient drug molecule to confer protection against inflammation is urgently needed.

Heterocyclic analogues and their derivatives have attracted strong interest in medicinal chemistry due to their biological and pharmacological properties. Benzothiazole is a class of heterocyclic compounds having 2 hetero atoms namely, sulphur and nitrogen. The analogues of benzothiazoles and its derivatives have a significant role in research area especially in synthetic, medicinal and pharmaceutical chemistry because of their biological and pharmacological activity. These compounds have special significance in the field of Medicinal chemistry due to their remarkable pharmacological potentialities. Benzothiazole is an organosulfur heterocyclic compound, weakly basic in nature. They are widely found in bioorganic and medicinal chemistry with wide application in drug discovery. Benzothiazoles are fused membered rings, which contain the heterocycles bearing thiazole as central moiety. A large number of therapeutic agents are synthesized with the help of benzothiazoles nucleus. In addition, benzothiazoles act as core nucleus in various drugs due to their various activities e.g. pramipexole, probenazole, lubeluzole, zopolrestat, ethoxazolamide and bentaluron etc. and their derivatives have attracted a great deal of interest due to their wide range of biological activities such as anticancer, antimicrobial, antitubercular, anti-HIV, cardiovascular, local anaesthetic, anti-inflammatory, anticonvulsant and anti-diabetic. The therapeutic properties of the heterocycles have encouraged the medicinal chemist to synthesize a large number of novel chemotherapeutic agents. This review is mainly an attempt to present the research work reported in the recent scientific literature focusing on different biological activities of benzothiazoles compounds.

Today it is well known about mechanisms of cell communication, how the cells that mediate immune response and tissue injury accumulate in tissues but the aetiology of rheumatoid arthritis (RA) is still unknown. This study was to evaluate immunomodulatory effects of crude Entamoeba histolytica (HM1 IMS strain) antigen in complete freund's adjuvant female wistar rats by studying the alterations in humoral and cell mediated immune responses and also the inflammatory effects by evaluating the changes in body weight, paw thickness, biochemical, serological, interleukin-6 (IL-6), IL-10 and tumor necrosis factor-? (TNF-?) and histopathology activities. Animals were randomly divided into six groups (n=6). CFA was induced in arthritic, drug and AA+CFA group whereas, 0.5ml amoebic antigen was induced subplantal in AA group while 0.5ml dose of amoebic antigen was given orally to AA+CFA group for 7-28th days. Indomethacin was used as a standard drug. Effects of amoebic antigen were associated with increased paw thickness and decreased body weight when compared to healthy control showed a significant difference. Oral administration of amoebic antigen has showed increased severe symptoms of arthritis in AA+CFA on comparison to healthy control rats. Significant increase in serum level of IL-6 and ? TNF were found in AA group followed by AA+CFA group whereas, decrease in concentration of IL-10 was appear in AA+CFA group on comparison to arthritic and healthy control group (P<0.05). Histopathology of AA group showed severe signs of necrotic and degenerative changes on comparison to healthy control group. Thus the results demonstrated that E. histolytica alone or in combination with CFA increased bone damage, with alterations in antioxidant level in liver and kidney tissue homogenates as well as showed immunomodulatory arthritogenic properties which may contribute and raise joint inflammation

A series of newer 3-(4'-methoxyphenyl)-5-substituted phenylisoxazoles derivatives have been synthesized by reacting hydroxylamine hydrochloride with chalcones. The chalcones were formed by reacting different aromatic aldehydes with 4-methoxyacetophenone in presence of aqueos potassium hydroxide (KOH). The purity of all the synthesized compounds was checked by recording their melting points and the retention Factors (Rf) values from thin layer chromatography. The structures of the compounds were characterized by recording their infrared (IR) spectra and confirmed by recording their nuclear magnetic resonance (1H NMR) spectra. The acute toxicity study was carried out on all the synthesized compounds and they were screened for their antiinflammatory activity by carrageenan induced rat paw edema method. Anti-inflammatory studies showed statistically significant activity when compared to the control, indomethacin. The two most potent compounds giving good anti-inflammatory activity were further evaluated for their antiulcer activity. The compounds were subjected to quantitative structure activity relationships (QSAR) studies. A close correlation between the observed and the predicted anti-inflammatory activity (Log % inhibition) for the compounds indicated the development of the best QSAR model. The synthesized compounds were found to be non-ulcerogenic as compared to the standard, aspirin.

Synthesis, Characterization and Screening for Analgesic and Anti-inflammatory activities of 2, 5-disubstituted 1, 3, 4-oxadiazole derivatives by Dhansay Dewangan, Kartik T. Nakhate, D. K. Tripathi, Pranita Kashyap, Hemant Dhongde (138-145).
The aim of the present investigation was to synthesize, characterize and evaluate analgesic and anti- inflammatory activities of 2, 5-disubstituted 1, 3, 4-oxadiazole derivatives. The reaction of starting material 4-chloro-m-cresol with ethyl chloroacetate in dry acetone affords ethyl (4-chloro-3-methylphenoxy) acetate, which after reacting with the hydrazine hydrate in ethanol yields 2(4-chloro-3-methylphenoxy) acetohydrazide. When 2(4-chloro-3-methylphenoxy) acetohydrazide was treated with different aromatic aldehydes, aromatic acids and carbon disulfide in alcoholic solution, different 3-acetyl-5-[(4-chloro-3-methylphenoxy) methyl]-2-aryl-2, 3-dihydro-1, 3, 4-oxadiazole and 2-[(4-chloro-3-methylphenoxy) methyl]-5-aryl-1, 3, 4-oxadiazole derivatives were obtained. Purity of the derivatives was confirmed by thin layer chromatography and melting point. Structure of these derivatives was set up by determining infrared spectroscopy, nuclear magnetic resonance spectroscopy and mass spectroscopy. Further, the synthesized derivatives were evaluated for their analgesic and anti-inflammatory activities in rodents. In animal studies, the derivatives 3-acetyl-5-[(4-chloro-3- methylphenoxy)methyl]-2-(4-methoxyphenyl)-2,3-dihydro-1, 3, 4-oxadiazole and 4-{5-[(4-chloro-3- methylphenoxy)methyl]-1, 3, 4-oxadiazol-2-yl}pyridine show more potent analgesic activity and the derivatives 2-{3-acetyl-5-[(4-chloro-3-methylphenoxy)methyl]-2,3-dihydro-1, 3, 4-oxadiazol-2-yl}phenol and 3-acetyl-5- [(4-chloro-3-methylphenoxy)methyl]-2-(4-methoxyphenyl)-2,3-dihydro-1, 3, 4-oxadiazole exhibit more potent anti-inflammatory effect as compared to other derivatives. The results of the current study indicate that cyclization of acetohydrazide produces novel oxadiazole derivatives with potent analgesic and anti-inflammatory activities.