A series of benzoxazole with thiazolidine derivatives were synthesized by the cyclization of substituted Schiff’s base with thioglycolic acid. The newly synthesized molecules were characterized by IR, 1 H NMR and mass spectral analysis. To all the compounds, the antibacterial, minimum inhibition concentration, antioxidant activity and molecular docking studies were evaluated. All synthesized benzoxazole with thiazolidine derivatives 6(a-j) exhibited promising antimicrobial activity against strains. The selected compound 6c, 6f, 6g, 6h, 6i and 6j was tested minimum inhibitory concentration, which showed good zone of inhibition at four different concentrations (25 µg/mL, 50 µg/mL, 75 µg/mL and 100 µg/mL) against gram positive and gram negative bacteria. The cytotoxicity of selected benzoxazole derivatives 6c, 6h, 6i and 6j displays potent activity against Peripheral Blood Mononuclear Cells. The synthesized compounds were introduced to DPPH free radical scavenging, in which the compounds 6c, 6e, 6g, 6h, 6i and 6j showed good free radical scavenging. The synthesized compounds were docked into the plausible target DPPH (PDB ID: 3MNG). The docking scores or the interaction binding energies of the target enzyme confirmed the antioxidant of the synthesized molecules. The final conclusion of the present work is benzoxazole linked thiazolidinine with qunoline derivatives such as 6g, 6h, 6i and 6j shows a effective antimicrobial , MIC, antioxidant activity and in silico molecular docking studies as compare to other derivatives, it is due to presence of combined effect of benzoxazole linked thiazolidinine with qunoline molecules.
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In general we know that the penicillin and cephalosporins like antibiotics contain thiazolidine ring systems, which are broad spectrum antibiotics. So, all the synthesized compounds of series (5a-f, containing thiazolidine ring) were screened against M. tuberculosis for their antitubercular activity and against some microorganisms for their antimicrobial activities. Generally compounds possessing electron withdrawing groups showed good antibacterial and antitubercular activity. Some derivatives (5b, 5c, 5d, 5e) containing electron withdrawing groups (-Cl, -Br, -NO 2 ) have shown promising activity against M. tuberculosis and some bacteria.
Biological Activities. The newly synthesized derivatives were evaluated for their in vitro antibacterial activity against E. Coli, P. Aeruginosa, S. Aureus, S. Pyogenes, S. typhi and V. parahaemolyticus by micro broth dilution methods . The standard strains used for screening of antibacterial and antifungal activities were procured from Institute of Microbial Technology (IMTECH), Chandigarh, India. The MIC values are given in Table 1. The standard drug used for antibacterial activity was ciprofloxacin. Mueller Hinton Broth was used as nutrient medium for bacteria and sabouraud dextrose broth for fungal to grow. Inoculums size for test strain was adjusted to 108 CFU/ mL by comparing the turbidity. The serial dilutions were prepared in primary and secondary screening. The target compounds and standard drugs were dissolved in DMSO-water (1:1 v/v) at a concentration of 2.0 mg/mL. In primary screening, 500 μg/mL, 250 μg/mL and 125 μg/mL concentrations of the synthesized drugs were taken. Data were not taken for the initial solution because of the high DMSO concentration (10%). The active synthesized drugs found in this primary screening were further tested in a second set of dilution against all microorganisms. In secondary screening, the drugs found active in primary screening were similarly diluted to obtain 100 μg/mL, 50 μg/ mL, 25 μg/mL, 12.5 μg/mL and 6.25 μg/mL concentrations. The inoculated wells were incubated overnight at 37°C in a humid atmosphere. The highest dilution showing at least 99% inhibition zone is taken as MIC.
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Heterocyclic chemistry comprises at least half of all organic chemistry research worldwide. The large numbers of biologically active molecules that contain heterocyclic rings has played important roles in the drug discovery process and exhibit various biological activities. A literature survey identified several thiazolidine derivatives in the development phase as potential new drugs. The versatility of the thiazolidine skeleton, in addition to its relative chemical simplicity and accessibility, makes these chemicals amongst the most promising sources of bioactive compounds. Numerous reports have appeared in the literature highlighting thiozolidine chemistry and its use. Thiazolidine possesses wide range of pharmacological activities viz.antibacterial  , cytotoxic  , anti-HIV  , antiviral  , anti- inflammatory  , anti-fungal  , anticonvulsant  , antioxidant  , antitumor  , antidiabetic  , antidepressant  etc.
Currently, heterocyclic compounds have been extensively studied due to their important properties and applications. Among these compounds, thiazol and thiazolidine derivatives have become especially noteworthy in recent years [1,2]. Thiazolidine derivatives has an interesting biological activities, some of these are anticancer activity [3,4], antioxidant  and also has an interesting antimicrobial activity [6,7].
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Thiazolidine derivatives possess antidiabetic and adipogenic properties (Norisada et al., 2004) and antitussive activity (Gandolfi et al., 1995). These derivatives induce insulin resis- tance via the normalization of protein-tyrosine phosphatase activities (Maegawa et al., 1995). Chromanone derivatives possess antiviral (Xu et al., 1998), antifungal (Emami et al., 2004; Yang et al., 2002) and anti-inflammatory (Konieczny et al., 1976) activities. The indole ring system is present in a number of natural products (Nigovic´ et al., 2000), many of which are found to possess psychotropic (Grinev et al., 1978) and antidepressant (Grinev et al. , 1984) properties. In view of its medicinal importance, the crystal structure and molecular structure determination of the title compound, (I), was carried out by X-ray diffraction.
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There are numerous biologically active molecules with five- membered rings containing two hetero atoms. Among them, thiazolidines are the most extensively investigated class of compounds (Fun et al., 2011). Thiazolidine derivatives have attracted continuous interest over the years because of their varied biological activities (Shih et al., 2015). The special importance of the thiazolidine ring system derives from the fact that it plays an important role in medicinal chemistry. The presence of a thiazolidine ring in penicillin and related derivatives was the first recognition of its occurrence in nature (C ˇ acˇic´ et al., 2010). Substituted thiazolidine derivatives represent important key intermediates for the synthesis of pharmacologically active drugs. The group has wide range of biological activities such as antifungal, antiproliferative, anti- inflammatory, antimalarial, herbicidal, antiviral (Samadhiya et al., 2012), anticonvulsant (Pandey et al., 2011), anticancer and anti-oxidant, and also has interesting antimicrobial activity (influenza). In addition, antidiabetic properties (Majed & Abid, 2015) have been reported. Thiazolidine derivatives exhibit anti-HIV, antituberculotic (Fun et al., 2011), herbicidal,
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biological activities such as antibacterial, insulin releasing, anti-inflammatory, and so on [19-21]. As we know, compounds including heterocyclic ring is of interest because of their ability to confer a wide range of biological and pharmacological properties . Some thiazolidine and its derivatives not only present effective anti-HIV  or anti-cancer [24,25] and cell division inhibition activities , but also in low toxicity.
Following these findings, our attention has been focused on a group of spirobenzothiophene- thiazolidinone derivatives (5a-e) and (6a-e). All the title compounds comprised four pharmacophoric elements that are necessary for good anticonvulsant activity. 19 These elements are present in many
Objective: Thiazolidine-2,4-dione (TZD) are the well known anti-diabetic scaffold. Very recently, several TZD based anti-cancer agents have came into limelight for treating mutant cancer forms. In order to establish and understand the relationship of biological activity with that of physiochemical parameters associated with the structure, two- dimensional (2D-QSAR), group-based (G-QSAR), and three-dimensional (3D-QSAR) were performed which may be useful for (medicinal) chemists in selecting the most suitable substituent for the development of more potent, effective and selective TZD based anticancer agents in future. Methods: A series of TZD derivatives were subjected to 2D-QSAR, G-QSAR, and 3D-QSAR studies. The following studies were performed using partial least square regression, multiple regressions and k-nearest neighbor methodology coupled with various feature selection methods, viz. stepwise forward backward (SWFB) and genetic algorithm (GA) to derive QSAR models which were further validated for statistical significance and predictive capability by internal and external validation. Results: The results were expressed for both SWFB and GA consecutively. The statistically significant best 2D QSAR model has r 2 =0.90, 0.89 and q 2 =0.86, 0.84
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Into a 100 ml clean and dry round bottom flask containing 10 ml of glacial acetic acid, introduced thiazolidene-2,4-dione (0.02 mol, 2.34 gm) (1), appropriate benzaldehyde (0.02 mol) and sodium acetate (0.015 mol, 2.46 gm) was added, the reaction mixture was refluxed for 12 h . After completion of reaction, the mixture was allowed to cool to room temperature and the separated solid was filtered, washed with water and dried. The obtained benzylidene derivatives (2a-2g) were recrystallized from ethanol , the yield was 65-90 %.
Although we desire to use L-cysteine HCl for our reaction for selective β-sulfhydryl protection as a free carboxy group is required for metal complexation. But the free carboxy group changes the reaction pH along with limiting its solubility to polar solvent like water thereby making the selective sulfhydryl protection unachievable with 2-(4-(bromomethyl)phenyl)isoindoline-1,3- dione 44 under basic conditions. Conversion of the L-cysteine hydrochloride 1 to the corresponding ethyl ester 21 led to selective β-sulfhydryl protection under basic conditions. The problem was the insolubility of L-Cysteine hydrochloride in organic solvents. Therefore, to improve Cysteine solubility it was converted to tosylate and long chain esters. One such example of L-cystiene tosylate 47 for selective sulfhydryl is outlined in Scheme 3.10. Selective β- sulfhydryl protection of L-cysteine using trityl chloride (Scheme 3.10) and benzoyl chloride were successfully accomplished using the ester 20 and the tosylate 47 of L-cysteine hydrochloride 1. These derivatives offered better solubility in organic solvents. The trityl group was found to be highly acid labile and unsuitable for peptide synthesis. For the desired peptide, synthesis at the N-terminal of compound 48 and 49 it was treated with a base. At this point, it was observed that the benzoyl group migrated from sulfur to the nitrogen to give compounds 78a and 78b. This is commonly known as Sulfur to Nitrogen migration. As Et 3 N was added, new
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In recent years, the spread of drug-resistant strains of Streptococcus pneumoniae, as the most common causes of bacterial respiratory infections, threatens public health. Therefore, the use of new antimicrobial medicines to inhibit this pathogen is an urgent demand. In this research project, the inhibitory effects of thirty recently synthesized compounds including thiazole, thiazolidine, imidazole, tetrahydropyrimidine, oxazolidine and thiazepine derivatives against this bacterium have been studied as well. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC), zone diameters of bacterial growth inhibition were also measured by a disk diffusion method. All the obtained results were compared with antibacterial effects of gentamicin and penicillin antibiotics. Among all investigated compounds, only derivatives 3d, 5a, 5b, 7, 9c, 15, 17c and 17d showed inhibitory effects against S. pneumonia. As a result, the most and least effects respectively belonged to thiazole derivative 15 and thiazepine derivative 17c with zone diameters of bacterial growth inhibition= 20.2, 9.3 mm, MIC= 64, 2048 μg/mL and MBC= 128, 4096 μg/mL. Whereas thiazole derivative 15 exhibited a good inhibitory activity against the mentioned pathogen, it can be replaced as a good agent instead of antibiotics.
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C57BL/KJ db/db mice and 10 weeks old C57BL/6J ob/ob mice. These compounds were fed via oral gavage at doses of 100- 200mg/kg. The experimental results of all compounds were compared with troglitazone (3) at 200mg/kg dose. On the basis of these experimental results, several compounds have shown similar or better blood glucose and triglyceride lowering activities as compared to troglitazone (3). Among these compounds, 5-[[4-[2-(1-indolyl)ethoxy]phenyl]methyl] thiazolidine-2,4-dione (21) was selected for further evaluation studies at different doses level in db/db and ob/ob mice. These results suggested that, compound (21) produced 60-70% reduction in blood glucose level after gave three days treatment at 50mg/kg dose. Similarly in ob/ob mice, a dose of 20mg/kg sufficiently normalize the blood glucose level. Finally, those studies indicated that compound (21) was far superior euglycemic and hypolipidemic agents as compared with troglitazone (3) 51 . Lohray et al reported the indole analogue of
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Melting points were determined by open capillary method and are uncorrected. The IR (KBr) spectra were recorded on thermo Nicolet IR-200 spectrophotometer. The 1 H-NMR spectra were recorded on varian NMR 400 MHz spectrometer using CDCL3 as a solvent and TMS as internal standard. The purity was conforimed by using TLC using suitable solvent system. Thiazolidine -4- one were prepared as the method of schiffs base as the synthetic procedures involved, the two steps as stated below.
As reported, the knoevenagel condensation of thiazolidine-2,4-diones have been carried out in a conventional synthesis. We initially synthesized four such derivatives via conventional method. As, we were interested in using solid-supported catalyst, silica-supported iodine along with base was used for knoevenagel condensation. Following scheme was visualized (Scheme 1).
Sixty four 2-(sub aryl)--(sub)thiazolidine-4-carboxamides were synthesized and evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB), and Mycobacterium smegmatis (MC 2 ).These compounds inhibited MTB with MICs of 0.12-20 µM and MC 2 with MICs of 1.23-29.80 µM. Among the synthesized compounds, compound (4-benzylpiperazin-1-yl)(2-(4- fluorophenyl)thiazolidin-4-yl)methanone 9b was found to be more potent with MIC of 0.12 µM against MTB and it was 5.5 and 1.9 times more potent than isoniazid and rifampicin respectively.
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anions could function as simple counter-ions to balance the charge on the metal or alternatively act as a ligand to the metal ion (Ferrer et al., 2000; Pal et al., 2005; Khavasi et al., 2011). However, the tzdSH ligand could also act as a reducing agent during the reaction, converting Cu II to Cu I and forming 3-(2- thiazolin-2-yl)thiazolidine-2-thione [tztzdt or C 6 H 8 N 2 S 3 ] in the
The present work discloses the synthesis of six novel benzylidene thiazolidine-2, 4-dione derivatives synthesized using 5-(4- hydroxybenzylidene) thiazolidine-2, 4-dione and their biological evaluation as anticancer and antidiabetic agents . The synthesized compounds were screened for PTP-1B inhibitory activity as well as anticancer activity. In this study we have used cancer cell lines DLD-1 and SW620 (colon cancer cell lines) and MCF-7 MDAMB-231 lines (breast cancer cell lines). For antidiabetic activity PTP 1B inhibitory action was observed and MIC values are found in µM concentration. Out of the screened compounds 5-(4-(prop-2-ynyloxy) benzylidene)-3- (prop-2-ynyl) thiazolidine-2, 4-dione (compound 9) was found to be active against PTP-1B and 5-(4-(7-chloroquinolin-4yloxy)benzylidene)thiazolidine-2,4-dione (compound 5) has been found to show activity against MDAMB-231 cell line as anticancer agent.
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9. Srikanth L., Raghunandan N., Srinivas P.and Amarender G. Reddy “Synthesis and Evaluation of newer Quinoline Derivatives of Thiazolidinediones for their Antidiabetic Activity” International Journal of Pharma and Bio Sciences, Vol.1 (4) 120-131(2010). 10. Ramachandran S. and Shanmugapandiyan P.