Synthesis, characterization, biological evaluation and in silico screening of oxadiazinanones (original) (raw)
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Molecules (Basel, Switzerland), 2015
With the aim of discovering new anticancer agents, we have designed and synthesized novel 6-hydroxy-benzo[d][1,3]oxathiol-2-one Schiff bases. The synthesis started with the selective nitration at 5-position of 6-hydroxybenzo[d][1,3]oxathiol-2-one (1) leading to the nitro derivative 2. The nitro group of 2 was reduced to give the amino intermediate 3. Schiff bases 4a-r were obtained from coupling reactions between 3 and various benzaldehydes and heteroaromatic aldehydes. All the new compounds were fully identified and characterized by NMR (1H and 13C) and specifically for 4q by X-ray crystallography. The in vitro cytotoxicity of the compounds was evaluated against cancer cell lines (ACP-03, SKMEL-19 and HCT-116) by using MTT assay. Schiff bases 4b and 4o exhibited promising cytotoxicity against ACP-03 and SKMEL-19, respectively, with IC50 values lower than 5 μM. This class of compounds can be considered as a good starting point for the development of new lead molecules in the fight a...
Medicinal Chemistry Research, 2016
New series of 1, 3, 4-oxadiazoles incorporating piperazine scaffolds in a single molecular framework has been reported. The structures of the synthesized derivatives were assigned by IR, NMR and mass spectral techniques. The hybrid compounds were evaluated for their antimicrobial, antitubercular and antioxidant activities. The observed MIC values of antitubular activities for the molecule 3a, 3b, 3c, 3d and 3e were 6.25, 3.12, 3.12, 1.60 and 50.0 µg/ml respectively. As compared to ascorbic acid (IC 50 = 62.91 µg/ml), molecule 3a exhibited better antioxidant activities (IC 50 = 36.72 µg/ml). Also, all molecules have shown significant antimicrobial activities. In addition, docking simulations were performed to study ligand-protein interactions and to determine the probable binding conformations. In drug likeness model study compound 3b possessed maximum drug likeness model score (0.75) similar to the standard drug streptomycin. The compound 3a, 3b and 3c were emerged as potential derivatives in the series and could serve as lead compound for the development of potential therapeutic agents.
Design, green synthesis, and anti-inflammatory activity of schiff base of 1,3,4-oxadiazole analogues
2014
Cyclooxygenase enzyme is a validated therapeutic target for designing drug molecules with anti-inflammatory activity. Herein, a series of various schiff base of 1,3,4-oxadiazole analogues were designed. Considering reasonable structural similarity of the target compounds with the commonly used anti-inflammatory drug indomethacin, it was decided to dock the target compounds into the active site of the molecular target of indomethacin. Prior to docking, the active sites of the proteins are identified. The docking study is performed using the UCSF DOCK 6.5 program. And also the utilization of principles involved in green chemistry is significantly reducing chemical waste and reaction times. To illustrate these advantages in the synthesis of bioactive oxadiazole derivatives, various environmentally benign protocols that involve greener alternatives were studied. The efficiency of microwave heating technology has resulted in remarkable reductions of reaction times (reduced from days and hours to minutes and seconds) with better product yield. The structures of newly synthesized compounds have been elucidated on the basis of IR, 1 H NMR, 13 C NMR, LC-MS and elemental analysis. An evaluation of the anti-inflammatory activity of the prepared compounds has indicated that some of them exhibited moderate to significant activity as compared to indomethacin.
Journal of emerging technologies and innovative research, 2020
A series of some 2-{(Z)-[(3-Methyl-5-sulfanyl-4H-1,2,4-triazol-4-yl)imino]methyl}-4H-chromen-4-ones were synthesized by reaction of substituted 4-oxo-4H-1-benzopyran-3-carbaldehyde with 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol in acidic medium. The synthesized compounds were characterized by proton NMR, 13C NMR, IR and mass spectroscopy techniques. The products were screened for their antioxidant and anti-inflammatory activities. Compound MP 2 and MP 6 demonstrate excellent antioxidant activity while remaining compounds show moderate activity. Compounds MP 2 and MP 3 demonstrate excellent anti-inflammatory activity while compounds MP 4, MP 6 and MP 8 show moderate activity.
International journal of Pharmacy and Pharmaceutical Sciences, 2014
Objective: In the present study, a series of novel 1,3,4-oxadiazole derivatives (3a-3q) were designed, synthesized and evaluated for antioxidant and anti-inflammatory activities. Methods: The title compounds were designed and docked onto the COX-2 enzyme (3LN1) protein using SYBYLX 2.1. 2-substituted-5-(5nitrobenzofuran-2-yl)-1,3,4-oxadiazole derivatives (3a-3p) were synthesized from acid catalyzed dehydrative cyclization of 5-nitrobenzofuran-2carbohydrazide (2) with various heteroaryl/aryl/aliphatic carboxylic acid derivatives. And 5-(5-nitrobenzofuran-2-yl)-1,3,4-oxadiazole-2-thiol (3q) was synthesized on reacting the hydrazide derivative 2 with carbon disulfide. The synthesized compounds were evaluated for in vitro antioxidant property by DPPH radical scavenging assay method and in vivo anti-inflammatory activity by carrageenan induced paw edema method. Results: The synthesized 1,3,4-oxadiazole derivatives (3a-3q) were characterized on the basis of LCMS, 1 HNMR [13]CNMR, IR and elemental analysis. The title compounds 3a-3q exhibited significant antioxidant efficacy ranging from 34 to 86%and the results of anti-inflammatory evaluation revealed that compounds 3c, 3e and 3d exhibited substantial anti-inflammatory activity of 72, 68 and 65%, respectively, at a dose of 50 mg kg-1. Conclusion: A significant correlation was observed between the in silico study and the anti-inflammatory results. The anti-inflammatory results highlight the synthesized compounds 3c, 3e and 3d could be considered as possible hit as therapeutic agents.
Oriental Journal Of Chemistry, 2012
Schiff bases or azomethines are an important class of compounds reported to possess carbon nitrogen double bond which is responsible for various biological activities 1 including antibacterial 2 , antifungal 3 , anti-inflammatory 4 , antipyretic 5 , antitumor 6,7 , anticancer 8 activities. They are also used as starting material for the synthesis of industrial 9 and biologically active â-lactum 10. Further Schiff bases have also been reported to possess chelatogenic properties, so form ligands in coordination chemistry 11-14. Various 1,3,4oxadiazoles have been reported to possess analgesic 15 , antihypertensive 16 , antifungal 15 , antiinflammatory 17 and anticancer 18 activities. Taking the above facts into consideration and our interest in the synthesis of biologically
Indian Journal of Pharmaceutical Education and Research
Introduction: Around 5,00,000 women are affected by cervical cancer and nearly half of them end up losing the battle of life with this deadly disease. So, there is an urgent need for the synthesis and development of new, small, synthetic molecules to tackle this challenge. Schiff's bases are derivatives of azomethine group (-CH=N-) and are highly reactive. Here a series of novel Schiff's bases were synthesized by single step process of condensing substituted 2-amino benzothiazole with different benzaldehydes. Objectives: To design, synthesize novel Schiff's bases of 2-amino benzothiazole and evaluate its anti-oxidant as well as anti-cancer activity. Methods: A total of 18 compounds were synthesized by single step process of condensing substituted 2-amino benzothiazole with different substituted benzaldehydes. These were characterized by FTIR, 1 H NMR, and Mass spectroscopy. The synthesized compounds were tested in-vitro for both antioxidant and antiproliferative activity. In-silico docking studies were performed on the crystal structure of the complex of caspase-3 with a nicotinic acid aldehyde inhibitor with PDB IDs 1RE1, 1RHM and 3DEH to study the interaction of the compounds with the receptor. Results: Majority of the derivatives displayed moderate to significant antiproliferative activity on HeLa cell line. Interestingly, the compound SP16 showed excellent activity with an IC 50 value of 2.517μg/ml in comparison to the reference compound Cisplatin (17.2μg/ml). Compound SP7 and SP 15 showed favourable in silico interactions.Conclusion: A series of 18 novel Schiff's bases of 2-amino benzothiazoles compounds were designed, synthesized and evaluated for their biological activities. The compound SP16 showed excellent activity with an IC 50 value of 2.517μg/ml in comparison to the reference compound Cisplatin and Compound SP7 and SP 15 showed favourable in silico interactions.
Journal of Pharmacy Research, 2017
Heterocyclic compounds have occupied a prominent place among various classes of organic compounds by virtue of their diverse biological activities and chemistry. Oxadiazoles are important pharmacophores in modern drug discovery. Among oxadiazoles, 1,3,4-oxadiazoles skeleton occupies a significant place in numerous bioactive molecules with a wide range of activities such as antimicrobial, anticancer, analgesic, anti-inflammatory, and anticonvulsant. The aim is to synthesize a drug with better efficacy, less toxicity, and fewer side effects. In view of the important biological activities in the present work, an attempt has been made to synthesize some novel oxadiazole derivatives and evaluate the biological profile of these compounds. The proposed molecules have been synthesized by reacting methyl salicylate and hydrazine hydrate which further reaction in the presence of carbon disulfide and potassium hydroxide yields 5-(2-hydroxyphenyl)-2-mercapto-1,3,4-oxadiazole derivatives of oxadiazoles were successfully obtained by condensation of mercapto oxadiazoles with different substituted aromatic carboxylic acids. The purity of the compounds was ascertained by melting point and thin-layer chromatography. The structures of the synthesized compounds have been characterized by the extensive use of Fourier transform infrared, H nuclear magnetic resonance, and mass spectral analysis. The title compounds were evaluated for antimicrobial and anti-inflammatory activities by the cup-plate method and carrageenan-induced rat paw edema method. All the test compounds exhibited pronounced antimicrobial and anti-inflammatory activity against the standards.
European Journal of Medicinal Chemistry, 2011
The synthesis of novel 2H-benzo [b][1,4]oxazin-3(4H)-one derivatives has been carried out using trifluoroacetic anhydride/phosphoric acid mediated CeC bond forming reaction as a key step. This method does not require the use of environmentally harmful AlCl 3 or moisture sensitive acid chloride. A number of compounds containing the benzooxazinone moiety attached to a five-membered central heterocyclic ring was synthesized and tested for their anti-cancer properties in vitro against three cell lines e.g. A549 (lung), DLD-1 (colorectal adenocarcinoma) and MV4-11 (acute myeloid leukemia). Some of them showed anti-cancer activities along with a number of reference compounds tested. Few of them showed promising anti-leukemic properties. A brief StructureeActivity-Relationship study within the series is presented. An imidazole derivative 9c containing benzene ring with a para-CF 3 group at C-2 position was identified as a potent anti-leukemic agent.
2011
Some novel Schiff bases derived from 1-(2-ketoiminoethyl)piperazines were synthesized and characterized by mass spectroscopy, FTIR, UV-Visible, (1)H and (13)C-NMR. The compounds were tested for inhibitory activities on human acetylcholinesterase (hAChE), antioxidant activities, acute oral toxicity and further studied by molecular modeling techniques. The study identified the compound (DHP) to have the highest activity among the series in hAChE inhibition and DPPH assay while the compound LP revealed the highest activity in the FRAP assay. The hAChE inhibitory activity of DHP is comparable with that of propidium, a known AChE inhibitor. This high activity of DHP was checked by molecular modeling which showed that DHP could not be considered as a bivalent ligand due to its incapability to occupy the esteratic site (ES) region of the 3D crystal structure of hAChE. The antioxidant study unveiled varying results in 1,1-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. This indicates mechanistic variations of the compounds in the two assays. The potential therapeutic applications and safety of these compounds were suggested for use as human acetylcholinesterase inhibitors and antioxidants.