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Thiazolidinones are well-known heterocycles that demonstrate promising biological effects such as anticonvulsant activity. Hybridization of these chemicals with scaffold, which has necessary pharmacophores for binding to the benzodiazepine receptors, can prompt a novel structure possessing extensive anticonvulsant effects. In this study, novel derivatives of thiazolidinone as new benzodiazepine agonists were designed, synthesized, and biologically evaluated. Compound 5h, 4-chloro-2-(2-fluorophenoxy)-N-(4-oxo-2-(p-tolyl)thiazolidin-3-yl)benzamide, exhibited considerable anticonvulsant activity, proper sedative-hypnotic effect, no memory impairment, and no muscle relaxant effect. The pharmacological effects of the designed compounds were antagonized by flumazenil, which confirmed the benzodiazepine receptors' involvement in their biological effects. Based on in silico calculations of ADME properties of our novel compounds, they could be active oral agents potentially. In this study, we designed novel structures by the hybridization of thiazolidinone moiety with scaffold which has necessary pharmacophores for binding to the benzodiazepine receptors. The results are very promising for developing new lead compounds as benzodiazepine agonists possess anticonvulsant effects.

QSAR modeling was performed on 39 quinolone-triazole derivatives against gram-positive Staphylococcus aureus and gram-negative Pseudomonas aeruginosa bacteria. The molecular structures were optimized using the DFT/B3LYP method and 6-31 G basis set. Molecular descriptors were extracted using quantum mechanical calculations. The hierarchical cluster analysis was performed for a rational subset division. The initial dataset was divided into calibration and validation sets, and modeling was done by stepwise MLR method for each of the two bacteria. Internal and external validation methods confirmed the robustness and predictability of the obtained models. According to the obtained model for S. aureus (R2 = 0.889, R2ext = 0.938, Q2LOO = 0.853), the four descriptors- partial atomic charges for the N1 atom in triazole and C7 of the quinolone nucleus, 4-carbonyl bond length, and 13C-NMR chemical shift of 3-carboxylic acid- were found to be the descriptors controlling the activity. According to the obtained model for P. aeruginosa (R2 = 0.957, R2ext = 0.923, Q2LOO = 0.909), the O atom's partial charge in carbonyl, LUMO-HOMO energy gap, and logP were found to be the descriptors having the highest correlation with the antibacterial activity. Finally, some new compounds with higher activities were designed and proposed.

Increasing diabetic population is one of the major health concerns all over the world. Inhibition of α-glucosidase is a clinically proved and attractive strategy to manage diabetes. In this study, robust and reliable QSAR models to predict α-glucosidase inhibitory potential of xanthone derivatives are developed by the Monte Carlo technique. The chemical structures are represented by SMILES notation without any 3D-optimization. The significance of the index of ideality correlation (IIC) with applicability domain (AD) is also studied in depth. The models developed using CORAL software by considering IIC criteria are found to be statistically more significant and robust than simple balance of correlation. The QSAR models are validated by both internal and external validation methods. The promoters of increase and decrease of activity are also extracted and interpreted in detail. The interpretation of developed models explains the role of different structural attributes in predicting the pIC50 of xanthone derivatives as α-glucosidase inhibitors. Based on the results of model interpretation, modifications are done on some xanthone derivatives and 15 new molecules are designed. The α-glucosidase inhibitory activity of novel molecules is further supported by docking studies.

Novel lead compounds as anticancer agents with the ability to circumvent emerging drug resistance have recently gained a great deal of interest. Thiazolidinones are among such compounds with well-established biological activity in the field of oncology. Here, we designed, synthesized and characterized a series of thiazolidinone structures (8a-8k). The results of anti-proliferative assay led to the discovery of compound 8j with a high potent cytotoxic effect using colon, liver and breast cancer cells. Furthermore, MDA-MB-231 and 4T1 cell lines were used to represent triple negative breast cancer (TNBC). Next, a number of in vitro and in vivo evaluations were carried out to demonstrate the potential activity against TNBC and also elucidate the possible mechanism of cell death induction. Our in vitro outcomes exhibited an impressive anticancer activity for compound 8j toward MDA-MB-231 cells through inducing apoptosis and a remarkable anti-metastatic feature via suppressing MMP-9 expression as well. Consistently, the in vivo and immunohistopathologic evaluations demonstrated that this compound significantly inhibited the 4T1 induced tumor growth and its metastasis to the lung. Altogether, among numerous thiazolidinone derivatives, compound 8j might represent a promising anticancer agent for TNBC, which is a major concern in the developed and developing countries.

A series of novel 1,3,4-thiadiazole derivatives bearing an amide moiety were designed, synthesized, and evaluated for their in vitro antitumor activities against HL-60, SKOV-3 and MOLT-4 human tumor cell lines by MTT assay. Ethyl 2-((5-(4-methoxybenzamido)-1,3,4-thiadiazol-2-yl)thio)acetate (5f) showed the best inhibitory effect against SKOV-3 cells, with an IC50 value of 19.5 μm. In addition, the acridine orange/ethidium bromide staining assay in SKOV-3 cells suggested that the cytotoxic activity of 5f occurs via apoptosis.

Background: Bacterial resistance to the available antibiotics is a life threatening issue and researchers are trying to find new drugs to overcome this problem. Amongst the different structural classes, thiazolidinone-4-one, as a new effective pharmacophore against various bacteria, has been introduced. Objective: A new series of 2-(5-(5-nitrothiophene-2-yl)-1,3,4-thiadiazole-2-ylimino)-5-arylidenethiazolidin- 4-one derivatives were designed and synthesized as new antibacterial agents. Method: Target compounds were synthesized during 5 steps and their in vitro antibacterial and anti-H. pylori activities were evaluated. The interaction of the most active derivatives with the probable targets was assessed by Auto Dock 4.2 Program. Results: The results showed that the most potent compounds, 18, 22 and 23, displayed antibacterial activity versus S.aureus, S.epidermidis, B.cereus and B.subtilis (MIC, 1.56-12.5 µg/mL) and none of the derivatives were active on tested Gram-negative bacteria. Compound 12 in all considered doses and compounds 10, and 27 had strong anti-H. pylori activity (inhibition zone >20 mm) in 25 μg disc. Docking studies determined suitable interactions and affinity of potent compounds with bacterial MUR B and H. pylori urease enzymes. Conclusion: According to the results most of the derivatives are effective anti-bacterial agents and docking evaluation confirmed their possible mechanisms of actions as MURB and Urease inhibitors.

The hydrazide backbone is a well-known structural core system found in a broad range of biologically activated compounds. Among which, the compounds with anticancer activity have been cited in a number of studies. With this object in mind, we focused on the in vitro and in vivo anticancer potential of two novel hydrazide derivatives bearing furan or thiophen substituents (compounds 1 and 2). The cytotoxic property was evaluated using MTT assay against MCF-7 human breast adenocarcinoma cell line, while the in vivo antitumor activity was investigated in BALB/c mice bearing 4T1 mammary carcinoma cells. Flow cytometry was used for cell cycle analysis, and detection of apoptosis was examined by Annexin-V-FLUOS/PI assay. Protein expression of Bax, Bcl-2 and procaspase-3 was estimated by Western blotting. Compounds 1 and 2 were found to be cytotoxic towards breast cancer cells presenting IC50 values of 0.7 and 0.18 µM, respectively, and selectivity over normal fibroblast cells. Our findings further indicated that 2 × IC50 concentrations of both compounds induce early stage apoptosis and increase percentage of sub-G1 population in MCF-7 cells at 48 h. An elevation in Bax/Bcl-2 ratio and caspase-3 cleavage suggested that apoptosis induced by the two compounds is through a caspase- and mitochondrial-dependent pathway. In the in vivo study, compounds 1 and 2 at doses of 10 and 1 mg/Kg/day, respectively, significantly hindered the growth of tumor after 3 weeks of i.p. administration, when compared to vehicle-treated mice. Collectively, the great potential exhibited by compound 2 could make it a promising chemotherapeutic candidate for human cancers, especially for breast cancer.

A series of new 1,3,4-oxadiazoles and 1,2,4-triazoles were synthesized in order to obtain new compounds with potential analgesic activity. Compounds were evaluated for their analgesic activities by formalin-induced nociception test. Mefenamic acid (as the reference drug) did not show any activity in the early phase of the formalin test, while compounds 7b, 7c, 8c, and 9a significantly reduced the nociception in this phase. However in the late phase of formalin test all of the target compounds and mefenamic acid showed analgesic activity in comparison to control.

A series of new arylidenehydrazone derivatives of naproxen were synthesized and evaluated for their analgesic and anti-inflammatory activities. Some of the synthesized analogues showed comparable activities when compared against naproxen for their analgesic and anti-inflammatory properties. 2-(6-methoxy-2-naphthyl)- N ′-[(pyridine-4-yl)methylene]propanoic acid hydrazide 4j was found to be the most active analgesic agent. 2-(6-methoxy-2-naphthyl)- N ′-[4-nitrobenzylidene]propanoic acid hydrazide 4g showed highest anti-inflammatory activity in comparison to the naproxen. Molecular modeling study of the synthesized compounds suggested that the designed molecules were well located and bound to the COX-1 and COX-2 active sites. Compound 4g showed the highest selectivity for COX-2 (R COX-2/COX-1 = 1.94) and higher affinity rather than naproxen in COX-2 active site (R COX-2/naproxen = 1.28). Moreover, the structural analyses confirmed that the E- ap rotamer is the preferred structure for the arylidenehydrazone derivatives.

In erythrocyte, catalase plays an important role to protect cells from hydrogen peroxide toxicity. Hydrogen peroxide is a byproduct compound which is produced during metabolic pathway of cells. Cimetidine, a histamine H2 receptor antagonist, is used for gastrointestinal tract diseases and prevents the extra release of gastric acid. In this study, the effect of cimetidine on the activity of human erythrocyte catalase was investigated. Erythrocytes were broken by hypotonic solution. The supernatant was used for catalase assay and kinetics study. Lineweaver-Burk plot was performed to determine the type of inhibition. The kinetics data revealed that cimetidine inhibited the catalase activity by mixed inhibition. The IC50 (1.54 μM) and Ki (0.45 μM) values of cimetidine determined that the drug was bound to the enzyme with high affinity. Circular dichroism and fluorescence measurement showed that the binding of cimetidine to the enzyme affected the content of secondary structure of the enzyme as well as its conformational changes. Docking studies were carried out to detect the site in which the drug was bound to the enzyme. Molecular modeling and energy calculation of the binding showed that the cyanoguanidine group of the drug connected to Asp59 via two hydrogen bonds, while the imidazole group of the drug interacted with Phe64 in the enzyme by a hydrophobic interaction. In conclusion, cimetidine could bind to human erythrocyte catalase, and its interaction caused functional and conformational changes in the enzyme.

Composition of a historical rose oil sample was investigated by GC and GC/MS. Forty-five components representing 95.5% composition of the essential oil were identified. The main components of this oil were citronellol (25.1%), geraniol (11.8%) and nonadecane (13.4%). The composition of the oil was compared with those of Turkish and Bulgarian rose oils and rose water.

The essential oils of Astrodaucus persicus (Boiss.) Drude were obtained by hydrodistillation of root and aerial parts and examined by GC and GC–MS. The composition of oil samples was compared; 22, 20 and 14 compounds were identified in the essential oils of the root, stem/leaves and flowers/fruits, representing 94.4%, 99.7% and 99.9%, respectively, of the total oils. The major components were bornyl acetate (26.5%), β-sesquiphellandrene (25.9%) and exo-fenchyl acetate (25.1%) for the root oil, α-pinene (56.4%) and exo-fenchyl acetate (37.7%) for the stem/leaves oil and β-pinene (46.1%), α-pinene (26.1%) and α-thujene (14.4%) for the flowers/fruits oil. The highest amount of sesquiterpenes was found in the root oil (30.7%). Copyright © 2005 John Wiley & Sons, Ltd.

A series of new 2-substituted-5-[2-(2-fluorophenoxy)phenyl]-1,3,4-oxadiazoles has been synthesized and screened for their anticonvulsant activities. Compound 3 shows considerable anticonvulsant activity both in PTZ and MES models. It seems that this effect is mediated by benzodiazepine receptors and other unknown mechanism, respectively.

Background Long-term clinical employment of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with significant side effects including gastrointestinal (GI) lesions and kidney toxicity. In this paper we designed and synthesized new imidazolyl-1,3,4-oxadiazoles and 1,2,4-triazoles by molecular hybridization of previously described anti-inflammatory compounds in the hope of obtaining new safer analgesic and anti-inflammatory agents. Methods The target structures were synthesized by preparation of 5-methyl-1H-imidazole-4-carboxylic acid ethyl ester 5. The reaction of hydrazine hydrate with this ester afforded the 5-methyl-1H-imidazole-4-carboxylic acid hydrazide 6 which was converted to target compounds 7-15 according to the known procedures. In silico toxicity risk assessment and drug likeness predictions were done, in order to consider the privileges of the synthesized structures as drug candidates. Results and discussion The analgesic and anti-inflammatory profile of the synthesized compounds were evaluated by writhing and carrageenan induced rat paw edema tests respectively. Compounds 8, 9 and 11-13 and 15 were active analgesic agents and compounds 8, 9 and 11-13 showed significant anti-inflammatory response in comparison with control. Compounds 11 and 13 were screened for their ulcerogenic activities and none of them showed significant ulcerogenic activity. The active Compounds 11 and 12 showed the highest drug likeness and drug score. Conclusions The analgesic and anti-inflammatory activities of title compounds were comparable to that of standard drug indomethacin with a safer profile of activity. The results revealed that both of oxadiazole and triazole scaffolds can be determined as pharmacophores. The in silico predictions and pharmacological evaluations showed that compounds 11 and 12 can be chosen as lead for further investigations.

A series of 2-phenoxybenzoic acid and N-phenylanthranilic acid hydrazides were synthesized and evaluated for their analgesic activities. Several compounds were significantly more potent than mefenamic acid and diclofenac sodium in abdominal constriction and formalin tests.