Aminothiazole Derivative Research Articles

Fluorinated azole anticancer drugs: Synthesis, elaborated structure elucidation and docking studies

The present article deals with the synthesis of novel nano-sized fluorinated thiazoles and studying their anticancer potentiality. The targeted azoles could be accessed via trifluoro-methylated thiosemicarbazone (3) prepared by reaction of with thiosemicarbazide in acidic solution of ethanol. The latter a fluorinated building block (3) have been reacted with appropriate derivatives of a-halo compounds namely, N-aryl 2-oxopropane-hydrazonoyl chlorides 4a-f using dioxane containing TEA as base catalyst. Also, the reaction between N-(4-(1-(2-carbamothioylhydrazineylidene)ethyl)phenyl)-2,2,2-trifluoroacetamide (3) and chloroacetonitrile 8 under the same experimental conditions furnished the corresponding amino thiazole derivative 11. In the same manner the base catalyzed cyclocondensation reaction between N-(4-(1-(2-carbamothioylhydrazineylidene)ethyl)phenyl)-2,2,2-trifluoroacetamide (3) and phenacyl bromide derivatives 12a-d afforded the corresponding thiazoles 13a-d in good yield. The structure of all synthesized thiazole derivatives as well as their mechanistic pathways were studied based on spectral data analysis and physical characteristics. The nanosized products were confirmed by using XRD analysis. Moreover, twelve samples were submitted for evaluation of their cytotoxicity activities against MDA-MB-231 (breast cancer cell) using colorimetric MTT assay, in comparison with Cisplatin standard drug. Two nano-sized thiosemicarbazone derivative 3 and the thiazole derivative 7c showed potent activity with IC50 = 7.7 and 2.97 µg/ml, respectively in compared with the IC50 = 4.33 µg/ml of cisplatin. The nanosized thiazole derivative 7c was more potent than cisplatin. Also, two thiazole derivatives 13b and 7b showed good activity with IC50 = 13.4 and 14.9 µg/ml. In addition, the molecular docking studies have been achieved using 4hy0, (X-chromosome-linked- inhibitor of apoptosis protein; (XIAP)).

Grafting of Thiazole Derivative on Chitosan Magnetite Nanoparticles for Cadmium Removal-Application for Groundwater Treatment.

The synthesis and developments of magnetic chitosan nanoparticles for high efficiency removal of the cadmium ions from aquatic medium are one of the most challenging techniques. Highly adsorptive composite (MCH-ATA) was produced by the reaction of chitosan with formaldehyde and amino thiazole derivative. The sorbent was characterized by FTIR, elemental analyses (EA), SEM-EDX, TEM analysis, TGA and titration (volumetric). The modified material includes high nitrogen and sulfur contents (i.e., 4.64 and 1.35 mmol g−1, respectively), compared to the pristine material (3.5 and 0 mmol g−1, respectively). The sorption was investigated for the removal of Cd(II) ions from synthetic (prepared) solution before being tested towards naturally contaminated groundwater in an industrial area. The functionalized sorbent shows a high loading capacity (1.78 mmol Cd g−1; 200 mg Cd g−1) compared to the pristine material (0.61 mmol Cd g−1; 68.57 mg Cd g−1), while removal of about 98% of Cd with capacity (6.4 mg Cd g−1) from polymetallic contaminated groundwater. The sorbent displays fast sorption kinetics compared to the non-modified composite (MCH); 30 min is sufficient for complete sorption for MCH-ATA, while 60–90 min for the MCH. PFORE fits sorption kinetics for both sorbents, whereas the Langmuir equation fits for MCH and Langmuir and Sips for MCH-ATA for sorption isotherms. The TEM analysis confirms the nano scale size, which limits the diffusion to intraparticle sorption properties. The 0.2 M HCl solution is a successful desorbing agent for the metal ions. The sorbent was applied for the removal of cadmium ions from the contaminated underground water and appears to be a promising process for metal decontamination and water treatment.

Synthesis and cytotoxic evaluation of some novel 3-[2-(2-phenyl-thiazol-4-yl)-ethyl]-3H-pyrido[2,3-d]pyrimidin-4-one derivatives.

Background and purpose:Pyridopyrimidine and its derivatives have a variety of chemical and biological significances. Thiazole-containing compounds have also been reported to have a wide range of biological activities. Due to the valuable cytotoxic effects of both thiazole and pyridopyrimidinone derivatives, a series of pyridopyrimidinone-thiazole hybrids were synthesized in the present study.Experimental approach:Briefly, different acyl chlorides were reacted with 2-amino nicotinic acid followed by anhydride acetic to give the corresponding pyridobenzoxazinones. The aminothiazole derivative G was also prepared via a multistep procedure and incorporated into the benzoxazinones to furnish the target pyridopyrimidinone, K1-K5. Furthermore, the cytotoxic activity of the final compounds was determined against MCF-7 and HeLa cell lines using MTT assay.Findings/Results:The results indicated that aromatic substitution on C2 of pyridopyrimidine nucleus was in favor of cytotoxic activity on both cell lines, of which, compound K5 bearing a chlorophenyl group showed the highest cytotoxicity.Conclusion and implications:The results of the present study are valuable in terms of synthesis of hybrid molecules and also cytotoxic evaluations which can be useful for future investigations about the design of novel pyridopyrimidinone-thiazole hybrids possessing better cytotoxic activities.

Crosstalks of the PTPIP51 interactome revealed in Her2 amplified breast cancer cells by the novel small molecule LDC3/Dynarrestin.

LDC3/Dynarrestin, an aminothiazole derivative, is a recently developed small molecule, which binds protein tyrosine phosphatase interacting protein 51 (PTPIP51). PTPIP51 interacts with various proteins regulating different signaling pathways leading to proliferation and migration. Her2 positive breast cancer cells (SKBR3) express high levels of PTPIP51. Therefore, we investigated the effects of LDC3/Dynarrestin on PTPIP51 and its interactome with 12 different proteins of various signal pathways including the interaction with dynein in SKBR3 cells. The localization and semi-quantification of PTPIP51 protein and the Tyr176 phosphorylated PTPIP51 protein were evaluated. Protein-protein-interactions were assessed by Duolink proximity ligation assays. Interactions and the activation of signal transduction hubs were examined with immunoblots. LDC3/Dynarrestin led to an increased PTPIP51 tyrosine 176 phosphorylation status while the overall amount of PTPIP51 remained unaffected. These findings are paralleled by an enhanced interaction of PTPIP51 with its crucial kinase c-Src and a reduced interaction with the counteracting phosphatase PTP1B. Furthermore, the treatment results in a significantly augmented interaction of PTPIP51/14-3-3β and PTPIP51/Raf1, the link to the MAPK pathway. Under the influence of LDC3/Dynarrestin, the activity of the MAPK pathway rose in a concentration-dependent manner as indicated by RTK assays and immunoblots. The novel small molecule stabilizes the RelA/IκB/PTPIP51 interactome and can abolish the effects caused by TNFα stimulation. Moreover, LDC3/Dynarrestin completely blocked the Akt signaling, which is essential for tumor growth. The data were compared to the recently described interactome of PTPIP51 in LDC3/Dynarrestin treated non-cancerous keratinocyte cells (HaCaT). Differences were identified exclusively for the mitochondrial-associated ER-membranes (MAM) interactions and phospho-regulation related interactome of PTPIP51.LDC3/Dynarrestin gives the opportunity/possibility to influence the MAPK signaling, NFkB signaling and probably calcium homeostasis in breast cancer cells by affecting the PTPIP51 interactome.

SYNTHESIS AND ANTIBACTERIAL PROPERTIES OF N,N-DISUBSTITUTED β-AMINO ACIDS CONTAINING FUNCTIONALIZED THIAZOLE FRAGMENT IN THE STRUCTURE

Aminothiazoles were synthesized from the thioureido acid and halo carbonyl compounds by the Hantzsch method. The bromination of thiazolone, performed in acetic acid at 30 °C, gave the expected product 3-[(5,5-dibromo-4-oxo-4,5-dihydrothiazol-2-yl)(4-methoxyphenyl)amino]propanoic acid. The methylene group in the five-membered heterocyclic ring easily participates in condensation reactions with carbaldehydes. All these reactions were carried out in a mixture of water and 2-propanol in the presence of sodium carbonate. The formed sodium salts were converted into acids by acidifying the reaction mixture with acetic acid to pH 6. The 3-[{5-[4-{[2-[(2-carboxyethyl)-(4-methoxyphenyl)amino]-4-oxo-1,3-thiazol-5(4H)-ylidene]methyl}phenyl)methylidene]-4-oxo-4,5-dihydro-1,3-thiazol-2-yl]-(4-methoxyphenyl)-amino]propanoic acid was obtained analogously to the above-mentioned method, only instead of carbaldehyde using dialdehyde terephthalaldehyde. The synthesized compounds 1-13 were evaluated for their antibacterial activity against the Xanthomonas campestris, Rhizobium radiobacter and Escherichia coli strains by the agar diffusion technique. Their activities were compared with those of the known antibacterial agent ampicillin (control C). The evaluation was performed at the Laboratory of Biotechnology of the Department of Organic Chemistry (Kaunas University of Technology). The growth of bacteria and the antibacterial activity were determined by using the Luria-Bertani (LB) nutrition media. The following concentrations of solutions in dimethyl sulfoxide were prepared: 1000, 500, 250, 125, 50 and 25 μg/ml. The prepared test-samples were incubated at 37 °C for 48 h. The effectiveness of the compounds was determined by measuring the zones of inhibition on a bacterial culture. The test cultures of E. coli appeared not to be sensitive to any concentration of the tested compounds. Nine of the thirteen compounds were inactive against the Xanthomonas campestris bacterium strain, and only four of them – the condensed aminothiazole derivative 3-[(4-methoxyphenyl)-(4,5,6,7-tetrahydrobenzothiazol-2-yl)amino]propanoic acid (4) and thiazolone derivatives 3-[(5,5-dibromo-4-oxo-4,5-dihydrothiazol-2-yl)(4-methoxyphenyl)amino]propanoic acid (6), (Z)-3-[(5-(4-bromobenzylidene)-4-oxo-4,5-dihydrothiazol-2-yl)(4- methoxyphenyl)amino]propanoic acid (8), and (Z)-3-[(5-(4-chlorobenzylidene)-4-oxo-4,5-dihydro-thiazol-2-yl)(4- methoxyphenyl)amino]propanoic acid (9) at a concentration of 1000 μg/ml inhibited the growth of the X. campestris strain. It should be noted that compound 9 (at the same concentration) was also active against the Rh. radiobacter bacterium strain. Hence, the results revealed the most effective compound – (Z)-3-[(5-(4-chlorobenzylidene)-4-oxo-4,5-dihydrothiazol-2-yl)(4-methoxyphenyl)amino]propanoic acid (9), which inhibited the growth of the Xanthomonas campestris and Rhizobium radiobacter bacteria strains.DOI: http://dx.doi.org/10.5755/j01.ct.68.1.18877

Determination of the binding site of 2-aminothiazole derivative with importin β1 by UV-crosslinking experiment.

Importin β1 (KPBN1) appears to be overexpressed in several cancer cells and siRNA-induced inhibition of KPNB1 shows significant inhibition of cancer cell proliferation, but do not affect normal cells. These results indicate that KPNB1 is a potential target and inhibition of KPNB1 can be used as a novel therapeutic approach for the treatment of cancer. Recently, we identified the aminothiazole derivative 1 as a KPNB1-targeted anticancer agent. Herein, we report that compound 1 binds strongly to KPNB1, in a pocket centered around serine-476, as shown by UV-crosslinking and tandem mass spectrometry experiments, and supported using a model derived from molecular docking.

Identification of KPNB1 as a Cellular Target of Aminothiazole Derivatives with Anticancer Activity.

We found that aminothiazole derivative (E)-N-(5-benzylthiazol-2-yl)-3-(furan-2-yl)acrylamide (1) has strong anticancer activity, and undertook proteomics approaches to identify the target protein of compound 1, importin β1 (KPNB1). A competitive binding assay using fluorescein-labeled 1 showed that 1 has strong binding affinity for KPNB1 (Kd : ∼20 nm). Furthermore, through western blotting assays for KPNB1, KPNA2, EGFR, ErbB2, and STAT3, we confirmed that 1 has inhibitory effects on the importin pathway. KPBN1 appears to be overexpressed in several cancer cells, and siRNA-induced inhibition of KPNB1 shows significant inhibition of cancer cell proliferation, while leaving non-cancerous cells unaffected. Therefore, compound 1 is a promising new lead for the development of KPNB1-targeted anticancer agents. Fluorescein-labeled 1 could be a useful quantitative probe for the development of novel KPNB1 inhibitors.

Design, synthesis, and biological evaluation of aminothiazole derivatives against the fungal pathogens Histoplasma capsulatum and Cryptococcus neoformans

Invasive fungal disease constitutes a growing health burden and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. Previously, an aminothiazole derivative, designated as 41F5, was identified in our laboratories as highly active against Histoplasma yeast (MIC50 0.4–0.8μM) through phenotypic high-throughput screening of a commercial library of 3600 purine mimicking compounds (Antimicrob. Agents Chemother.2013, 57, 4349). Consequently, 68 analogues of 41F5 were designed and synthesized or obtained from commercial sources and their MIC50s of growth inhibition were evaluated in Histoplasma capsulatum to establish a basic structure–activity-relationship (SAR) for this potentially new class of antifungals. The growth inhibiting potentials of smaller subsets of this library were also evaluated in Cryptococcus neoformans and human hepatocyte HepG2 cells, the latter to obtain selectivity indices (SIs). The results indicate that a thiazole core structure with a naphth-1-ylmethyl group at the 5-position and cyclohexylamide-, cyclohexylmethylamide-, or cyclohexylethylamide substituents at the 2-position caused the highest growth inhibition of Histoplasma yeast with MIC50s of 0.4μM. For these analogues, SIs of 92 to >100 indicated generally low host toxicity. Substitution at the 3- and 4-position decreased antifungal activity. Similarities and differences were observed between Histoplasma and Cryptococcus SARs. For Cryptococcus, the naphth-1-ylmethyl substituent at the 5-position and smaller cyclopentylamide- or cyclohexylamide groups at the 2-position were important for activity. In contrast, slightly larger cyclohexylmethyl- and cyclohexylethyl substituents markedly decreased activity.

Synthesis and antimicrobial activity of some isoindole derivatives

Oxoisoindolium hexachloroantimonate 1a was reacted with different nitriles to afford 2-azoniaallene salts. These underwent cyclization on heating, furnishing tetracyclic compounds 2a, b. Oxoisoindolo[2,1-a]quinazolinium hexachloroantimonate 3 reacted with p-toluidine to afford the corresponding salt 4. This was neutralized with sodium carbonate to give the corresponding free base 5. Isoindolo[2,1-a]quinazoline derivative 6 was prepared by treatment of 3 with benzohydrazide in dichloroethane. Reaction of the extremely sensitive salt of oxoisoindolium 1 with aminothiazole derivative 7 afforded the formal salts of 2-azoniaallene 8. Neutralization of these afforded the corresponding free base 9. The structures of the synthesized compounds were confirmed by IR, 1H NMR, 13C NMR, and mass spectroscopy. The free base compounds were screened for antimicrobial activity.

Protective effect of dendrodoine analog, an aminothiazole derivative against X-radiation induced hepatocellular damage in mice

This study evaluated the radioprotective effect of dendrodoine analog (DA) against radiation-induced damage in the liver of mice. The study was divided into two phases; in the first phase, the effective concentration of DA was fixed by performing a survival study. In the second phase, the fixed effective concentration of DA was orally administered to mice to evaluate its radioprotective efficacy by performing various assays. The results indicated that the radiation-induced decrease in the activities of antioxidant enzymes, increase in thiobarbituric acid reactive substances (TBARS) and comet parameters were altered by pre-administration with the effective concentration of DA which restored the antioxidant status to near normal and decreased the level of the TBARS and comet parameters. The histopathological examinations further confirmed the hepatoprotective effect of DA in mice. Thus, the current study showed DA to be an effective radioprotector against radiation induced damage in the liver of mice.

Evaluating the Radioprotective Efficacy of Dendrodoine Analog Against the Formation of Dicentric Aberration Frequency in Cultured Human Peripheral Blood Lymphocytes

The present study was aimed to evaluate the protective efficacy of dendrodoine analog (DA), an aminothiazole derivative against the formation of radiation induced dicentric (DC) aberration frequency on cultured human peripheral blood lymphocytes. DA was chemically synthesized and the product thus obtained was purified using column chromatography packed with silica gel using chloroform as the solvent. The purity status of the final product was assessed employing high performance thin layer chromatography (HPTLC). The radioprotective efficacy of DA against the formation of DC aberration frequency was analyzed by pre-incubating human peripheral blood lymphocytes with the optimum concentration of DA, selected from our previous study, followed by exposure to different doses of radiation. The results indicated that there was a dose dependent increase in the formation of DC aberration frequency in the irradiated groups when compared to DA pre-treated groups which modulated the toxic effects of radiation by means of its effective DNA protective and antioxidant property.

ChemInform Abstract: A Novel Aminothiazole Derivative Induces Apoptosis and Cell Cycle Arrest in Tumor Cells.

AbstractCompound (I), found in a cell‐based high‐throughput screening, exhibits significant cell growth inhibition against HepG2 cells.

A Novel Aminothiazole Derivative Induces Apoptosis and Cell Cycle Arrest in Tumor Cells

Compound (I), found in a cell-based high-throughput screening, exhibits significant cell growth inhibition against HepG2 cells.

Protection against X-ray radiation-induced cellular damage of human peripheral blood lymphocytes by an aminothiazole derivative of dendrodoine

The present study was aimed to evaluate the radioprotective efficacy of dendrodoine analog (DA), an aminothiazole derivative against X-ray radiation-induced cellular damage in cultured human peripheral blood lymphocytes. Different concentrations of DA (2, 4, 6, 8, 10 μg/ml or 6.15, 12.29, 18.44, 24.59, 30.73 μM) were pre-incubated with lymphocytes for 30 min prior to irradiation [4 Gy] and the micronuclei (MN) scoring and comet assay were performed to fix the effective concentration of DA against 4 Gy irradiation-induced cellular damage. The results indicated that among all the concentrations, 6 μg/ml concentration of DA showed optimum protection by effectively decreasing the MN frequencies and comet attributes. Based on the above results, 6 μg/ml concentration of DA was fixed as the effective dose to further investigate its radioprotective efficacy. This was carried out by pre-incubating the lymphocytes with 6 μg/ml concentration of DA followed by exposure of the lymphocytes to different doses (1, 2, 3 and 4 Gy) of radiation and investigating the radiation-induced genetic damage (MN, comet assay, DNA fragmentation assay) and biochemical changes (changes in the level of enzymic and non-enzymic antioxidants, lipid peroxidation). The results indicated a dose-dependent increase in both genetic damage and thiobarbituric acid reactive substances (TBARS), accompanied by a significant decrease in the antioxidant status in the irradiated groups compared to DA treated groups which modulated the toxic effects through its antioxidant potential. Thus the current study shows DA to be an effective radioprotector against X-ray radiation induced in vitro cellular damage in lymphocytes.

Antioxidant potential of aminothiazole derivative and its protective effect on H2O2-induced oxidative damage on pBR322 DNA and RBC cellular membrane

The present work was carried out to evaluate the antioxidant and free radical scavenging activity of aminothiazole derivative by performing various in vitro assays; to study its protective effect on H(2)O(2)-induced oxidative damage on pBR322 DNA and on RBC cellular membrane. The in vitro assays were performed with different concentrations of aminothiazole derivative (6.15, 12.29, 18.44, 24.59, and 30.73 microM) and the results were compared with standards like ascorbic acid and trolox. Our results clearly indicated that aminothiazole derivative at a dose of 18.44 microM exhibited radical scavenging activity greater than that of ascorbic acid and trolox. The DNA protective effect on pBR322 DNA showed that there was a concentration-dependent inhibition of the disappearance of supercoiled (ccc) form of DNA on incubation with 30 mM H(2)O(2) in the presence of different concentrations of aminothiazole derivative. Thus our compound at 1.5 mM prevents the conversion from supercoiled (ccc) form to open circular form (oc) form of pBR322 DNA. Pretreatment with aminothiazole derivative at a dose of 18.44 microM prevents membrane damage and exhibits an IC(50) value, which is the concentration of the sample required to inhibit 50% of the radical formed greater than that of the standards (ascorbic acid and trolox). Thus our compound of interest aminothiazole derivative exhibits antioxidant and free radical scavenging properties greater than that of standards like ascorbic acid and trolox and thereby protects pBR322 DNA and RBC cellular membrane from free radical induced oxidative damage.

Antioxidant activity of an aminothiazole compound: Possible mechanisms

Oceans are among the richest natural sources of many bioactive compounds. Several of these compounds have shown pharmacological activities for many diseases. Dendrodoine (5-[(3- N-dimethylamino)-1,2,4-thiadiazolyl]-3-indanyl methanone) is an alkaloid extracted from the marine tunicate Dendrodoa grossularia. Aminothiazoles have a wide range of biological activities including anti-tumor and antioxidant properties. The aim of our study was to examine the antioxidant ability of an aminothiazole derivative, dendrodoine analogue (DA) [(4-amino-5-benzoyl-2-(4-methoxy phenylamino) thiazole] which has been chemically synthesized and is similar to dendrodoine. In all the biochemical assays used in our study, corresponding to different levels of protection, DA showed concentration dependent antioxidant ability. DA (3.07 μM) showed an ability to inhibit 2,2′-azobis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) radical formation to the extent of 0.17 μM of 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). The ferric complex reducing ability of 3.07 μM DA was equivalent to 110 μM Trolox. 3.07 μM DA gave 84% protection against deoxyribose degradation, a measure of hydroxyl radical scavenging. DA also has an ability to scavenge NO radical, 3.07 μM DA effecting 20% scavenging. Concentration dependent inhibition of lipid peroxidation and protein oxidation induced by 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH) and ascorbate-Fe 2+ was observed with low concentrations of DA (1.5–3.07 μM). Mechanistic studies using pulse radiolysis revealed that DA scavenges peroxyl radicals with a bimolecular rate constant of 3 × 10 8 M −1 s −1. Moreover, the initially formed nitrogen-centered radical gets transformed into sulfur-centered radical before furnishing any final product. Our results indicated that DA can be a free radical scavenger and potential antioxidant for future application.

Structure-assisted discovery of an aminothiazole derivative as a lead molecule for inhibition of bacterial fatty-acid synthesis.

Fatty-acid synthesis in bacteria is of great interest as a target for the discovery of antibacterial compounds. The addition of a new acetyl moiety to the growing fatty-acid chain, an essential step in this process, is catalyzed by beta-ketoacyl-ACP synthase (KAS). It is inhibited by natural antibiotics such as cerulenin and thiolactomycin; however, these lack the requirements for optimal drug development. Structure-based biophysical screening revealed a novel synthetic small molecule, 2-phenylamino-4-methyl-5-acetylthiazole, that binds to Escherichia coli KAS I with a binding constant of 25 microM as determined by fluorescence titration. A 1.35 A crystal structure of its complex with its target reveals noncovalent interactions with the active-site Cys163 and hydrophobic residues of the fatty-acid binding pocket. The active site is accessible through an open conformation of the Phe392 side chain and no conformational changes are induced at the active site upon ligand binding. This represents a novel binding mode that differs from thiolactomycin or cerulenin interaction. The structural information on the protein-ligand interaction offers strategies for further optimization of this low-molecular-weight compound.

Synthesis of 2-Amino-5-arylthiazoles by Palladium-Catalyzed Arylation at the C5 Position with Aryl Iodides

A new synthetic route to afford 2-amino-5-aryl thiazoles has been developed. The starting aminothiazole derivative can be arylated at position 5 with aryl iodides under palladium-catalyzed conditions. Mechanistic studies suggest a proton-abstraction pathway for this transformation.

Role of an Aminothiazole Derivative on Ethanol-Induced Toxicity

ABSTRACTThe protective effect of dendrodoine analog (DA) [4-amino-5-benzoyl-2-(4-methoxy phenylamino) thiazole] at three doses (5, 10, and 15 mg/kg body weight) was investigated on ethanol-induced hyperlipidemia. Hepatotoxicity was induced by administering 7.9 g ethanol/kg body weight for 45 days by intragastric intubation. Our results showed increased activity of aspartate transaminase (AST), alkaline phosphatase (ALP), and gamma glutamyl transferase (GGT) and increased levels of cholesterol, triglycerides, and phospholipids in the plasma of alcohol-given group when compared with normal control group. The levels of tissue (liver and kidney) cholesterol and triglycerides were increased significantly in alcohol control rats when compared with normal control rats. The levels of phospholipids decreased significantly in the liver and kidney of alcohol control rats when compared with normal control rats. The activity of phospholipase A and phospholipase C increased significantly in the liver of alcohol control rats when compared with normal control rats. Intragastric administration of DA at 10 mg/kg body weight effectively lowered the activity of hepatic marker enzymes (GGT, AST, and ALP), phospholipase A, and phospholipase C, and decreased the levels of plasma and tissue lipids. The level of tissue phospholipids increased significantly when DA was administered at a dose of 10 mg/kg body weight along with alcohol when compared with alcohol control group. Thus, we propose that DA exerts a hepatoprotective effect by modulating liver marker enzymes and lipid levels at a dosage of 10 mg/kg body weight.

Expression Pattern of Matrix Metalloproteinases in Alcohol- and Thermally Oxidized Sunflower Oil-Induced Toxicity: Protective Role of an Aminothiazole Derivative

The matrix metalloproteinases (MMPs) are a family of secreted and membrane-bound zinc endopeptidases. Collectively, these enzymes can degrade all of the components of the extracellular matrix including collagen, fibronectin, laminin, and basement membrane glycoproteins. Regulation in expression and activation of proteinases is one of the most important mechanisms in organ morphogenesis. Fibrosis is a dynamic pathological process with a net accumulation of extracellular matrix proteins. In the present communication, we have investigated the changes that occur in the activity of liver MMPs in normal and in pathological conditions. The activity of MMPs was increased in thermally oxidized sunflower oiland alcohol-treated groups, whereas the activity was decreased in the thermally oxidized oil + alcohol-fed group when compared with the normal control group. The activity was positively modulated when dendrodoine analogue [4-amino-5-benzoyl- 2(4-methoxyphenylamino)thiazole] was administered along with ethanol and thermally oxidized oil, which indicates the protective effect of this drug.