Synthesis, characterization and biological investigations of potentially bioactive heterocyclic compounds containing 4-hydroxy coumarin.
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ABSTRACT:
SUBMITTER: Nagaraja O
PROVIDER: S-EPMC7330081 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe derivatives of thieno[2,3-b]thiophene belong to a significant category of heterocyclic compounds, which have shown a wide spectrum of medical and industrial application.ResultsA new building block with two electrophilic center of thieno[2,3-b]thiophene derivatives 2 has been reported by one-pot reaction of diketone derivative 1 with Br2/AcOH in excellent yield. A variety of heteroaromatics having bis(1H-imidazo[1,2a] benzimidazole), bis(1H-imidazo[1,2-b][1,2,4]triazole)-3-methyl-4-phenylthieno[2,3-b]thiophene derivatives, dioxazolo-, dithiazolo-, and 1H-imidazolo-3-methyl-4-phenylthieno[2,3-b]thiophene derivatives as well pyrrolo, thiazolo -3-methyl-4-phenylthieno[2,3-b]thiophene derivatives have been designed, synthesized, characterized, and evaluated for their biological activity. Compounds 3-9 showed good bioassay result. These new derivatives were evaluated for anti-cancer activity against PC-3 cell lines, in vitro antioxidant potential and ?-glucuronidase and ?-glucosidase inhibitory activities. Compound 3 (IC50?=?56.26?±?3.18??M) showed a potent DPPH radical scavenging antioxidant activity and found to be more active than standard N-acetylcystein (IC50?=?105.9?±?1.1??M). Compounds 8a (IC50?=?13.2?±?0.34??M) and 8b (IC50?=?14.1?±?0.28??M) found as potent inhibitor of ?-glucusidase several fold more active than the standard acarbose (IC50?=?841?±?1.73??M). Most promising results were obtained in ?-glucuronidase enzyme inhibition assay. Compounds 5 (IC50?=?0.13?±?0.019??M), 6 (IC50?=?19.9?±?0.285??M), 8a (IC50?=?1.2?±?0.0785??M) and 9 (IC50?=?0.003?±?0.09??M) showed a potent inhibition of ?-glucuronidase. Compound 9 was found to be several hundred fold more active than standard D-Saccharic acid 1,4-lactone (IC50?=?45.75?±?2.16??M).ConclusionsSynthesis, characterization, and in vitro biological activity of a series of thieno[2,3-b]thiophene have been investigated.
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Project description:We report the synthesis, structural characterization and pharmaceutical activity of four coumarin-quinone hybrids. The compounds were significantly active against Staphylococcus aureus, Pseudomonas aeoginosa and Candida albicans. Promising antioxidant activity was observed when compared to ascorbic acid. Two compounds, DTBSB and DTBSN, also showed commendable in vitro antiproliferative activities against the cells of human cancer cell lines MCF-7, MDA-MB-231, COLO-205, HT-29 and A549 along with appreciable tumor selectivity with distinct selectivity index. Molecular docking studies using cyclooxygenase-2 (PDB ID: 6COX) revealed strong binding affinities for the COX-2 active site. Moreover, ADMET properties of the synthesized compounds were determined using the pKCSM and SwissADME online tools and all the compounds had accurate pharmacokinetic profiles. Hence, the new coumarin-quinone hybrids DTBSB and DTBSN can be considered for optimization and lead development.
| S-EPMC9909729 | biostudies-literature
Project description:A series of new coumarin containing compounds were synthesized from 4-bromomethylcoumarin derivatives 2a, b and different heteroaromatic systems 4a-e, 6a-d, 8, 10via methylene thiolinker. Twenty-four compounds were screened biologically against two human tumor cell lines, breast carcinoma MCF-7 and hepatocellular carcinoma HePG-2, at the national cancer institute, Cairo, Egypt using 5-fluorouracil as standard drug. Compounds 5h, 7d, 7h, 9a, 13a and 13d showed strong activity against both MCF-7 and HepG-2 cell lines with being compound 13a is the most active with IC50 values of 5.5 µg/ml and 6.9 µg/ml respectively. Docking was performed with protein 1KE9 to study the binding mode of the designed compounds.
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Project description:Currently, there is a growing interest in the synthesis of heterocyclic compounds containing hydroquinoline fragments. This surge can be attributed to the broad range of pharmaceutical and industrial applications that these compounds possess. In this study, the synthesis of both linear and fused heterocyclic systems that incorporate hydroquinoline fragments was described. Furthermore, the pharmacological activity spectra of the synthesized compounds were predicted using the in silico method, employing the Prediction of Activity Spectra of Substances (PASS) program. Hydroquinolines containing the nitrile functionality 7 and 8 were synthesized through the reaction of the corresponding hydroquinolinecarbaldehyde 5a, 6b with hydroxylamine hydrochloride and iodine in aqueous ammonia under ambient conditions, respectively. 2-Phenyl-1,3-oxazol-5(4 H)-ones 9a, b and 10a, b were synthesized via the condensation of compounds 5a, b and 6a, b with hippuric acid in acetic acid in 30-60% yield. When the methyl activated 7-methylazolopyrimidines 11a, b were reacted with N-alkyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline-6-carbaldehydes 6a, b, 60-70% yield of triazolo/pyrazolo[1,5-a]pyrimidin-6-yl carboxylic acids 12a, b were obtained. The condensation of 7-hydroxy-1,2,3,4-tetramethyl-1,2-dihydroquinoline 3 h with dimethylacetylenedicarboxylate (DMAD) and ethyl acetoacetate afforded cyclic products 16 and 17, respectively. The condensation reaction of 6-formyl-7-hydroxy-1,2,2,4-tetramethyl-1,2-dihydroquinoline 5e with methylene-active compounds such as ethyl cyanoacetate/dimethyl-3-oxopentanedioate/ethyl acetoacetate/diethylmalonate/Meldrum's acid afforded 3-substituted coumarins 19 and 21 containing dihydroquinoline moiety. The pentacyclic coumarin 22 was obtained via the tandom condensation reaction of malononitrile with 5e in the presence of a catalytic amount of piperidine in ethanol. The biological activities of the synthesized compounds were predicted using the PASS program. Based on the prognosis, compounds 13a, b, and 14 exhibited a high likelihood of being active as inhibitors of gluconate 2-dehydrogenase, as well as possessing antiallergic, antiasthmatic, and antiarthritic properties, with a probability value (Pa) ranging from 0.849 to 0.870. Furthermore, it was discovered that compounds 7 and 8 tended to act as effective progesterone antagonists and displayed antiallergic, antiasthmatic, and antiarthritic effects (Pa = 0.276-0.827). Among the hydroquinolines containing coumarin moieties, compounds 17, 19a, and 19c were predicted to be potent progesterone antagonists, with Pa values of 0.710, 0.630, and 0.615, respectively.
| S-EPMC11363556 | biostudies-literature
Project description:[1,3,5]Triazino[1,2-a]benzimidazole-2-amines bearing heterocyclic moiety in 4-position were synthesized. The compounds were characterized by elemental analysis, IR, 1H-NMR, 13C-NMR, and HRMS spectroscopy. The molecular geometry and electron structure of these molecules were theoretically studied using density functional theory (DFT) methods. The molecular structure of the synthesized fused triazinobenzimidazole was confirmed to correspond to the 3,4-dihydrotriazinobenzimidazole structure through the analysis of spectroscopic NMR data and DFT calculations. The antinematodic activity was evaluated in vitro on isolated encapsulated muscle larvae (ML) of Trichinella spiralis. The results showed that the tested triazinobenzimidazoles exhibit significantly higher efficiency than the conventional drug used to treat trichinosis, albendazole, at a concentration of 50 μg/mL. The compound 3c substituted with a thiophen-2-yl moiety exhibited the highest anthelmintic activity, with a larvicidal effect of 58.41% at a concentration of 50 μg/mL after 24 h of incubation. Following closely behind, the pyrrole analog 3f demonstrated 49.90% effectiveness at the same concentration. The preliminary structure-anti-T. spiralis activity relationship (SAR) of the analogues in the series was discussed. The cytotoxicity of the benzimidazole derivatives against two normal fibroblast cells (3T3 and CCL-1) and two cancer human cell lines (MCF-7 breast cancer cells and chronic myeloid leukemia cells AR-230) was evaluated using the MTT-dye reduction assay. The screening results indicated that the compounds showed no cytotoxicity against the tested cell lines. An in silico study of the physicochemical and pharmacokinetic characteristics of the novel synthesized fused triazinobenzimidazoles showed that they were characterized by a significant degree of drug-likeness and optimal properties for anthelmintic agents.
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Project description:Lanthanoid-containing polyoxometalates (Ln-POMs) have been developed as effective and robust catalysts due to their Lewis acid-base active sites including the oxygen-enriched surfaces of POM and the unique 4f. electron configuration of Ln. As an extension of our interest in Ln-POMs, a series of as-synthesized nanocatalysts K15[Ln(BW11O39)2] (Ln-B2W22, Ln = La, Ce, Nd, Sm, Gd, and Er) synthesized and fully characterized using different techniques. The Ln3+ ion with a big ionic radius was chosen as the Lewis acid center which is sandwiched by two mono-lacunary Keggin [BW11O39]9- units to form Ln-containing sandwiched type cluster. Consequently, the catalytic activity of nanocatalysts with different Ln was examined in the synthesis of bioactive isatin derivatives and compared under the same optimized reaction conditions in terms of yields of obtained products, indicating the superiority of the nano-Gd-B2W22 in the aforementioned simple one-pot reaction. The effects of different dosages of nanocatalyst, type of solvent, reaction time, and reaction temperature in this catalytic system were investigated and the best results were obtained in the presence of 10 mol% of nano-Gd-B2W22 in water for 12 min at the reflux condition.
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Project description:Half-sandwich Ru(II) complexes belong to group of biologically active metallo-compounds with promising antimicrobial and anticancer activity. Herein, we report the synthesis and characterization of arene ruthenium complexes containing benzimidazole moiety, namely, [(η6-p-cymene)RuCl(bimCOO)] (1) and [(η6-p-cymene)RuCl2(bim)] (2) (where bimCOO = benzimidazole-2-carboxylate and bim = 1-H-benzimidazole). The compounds were characterized by 1H NMR, 13C NMR, IR, UV-vis and CV. Molecular structures of the complexes were determined by SC-XRD analysis, and the results indicated the presence of a pseudo-tetrahedral (piano stool) geometry. Interactions in the crystals of the Ru complexes using the Hirshfeld surface analysis were also examined. In addition, the biological studies of the complexes, such as antimicrobial assays (against planktonic and adherent microbes), cytotoxicity and lipophilicity, were performed. Antibacterial activity of the complexes was evaluated against S. aureus, E. coli, P. aeruginosa PAO1 and LES B58. Cytotoxic activity was tested against primary human fibroblasts and adenocarcinoma human alveolar basal epithelial cells. Obtained biological results show that the ruthenium compounds have bacteriostatic activity toward Pseudomonas aeruginosa PAO1 strain and are not toxic to normal cells. A molecular docking study was applied as a predictive source of information about the plausibility of examined structures binding with HSA as a transporting system.
| S-EPMC9821818 | biostudies-literature
Project description:We report here a practical and metal-free synthesis of novel enantiopure amides containing the drug-like 5-nitroimidazole scaffold. The first step was a metal-free diastereoselective addition of 4-(4-(chloromethyl)phenyl)-1,2-dimethyl-5-nitro-1H-imidazole to enantiomerically pure N-tert-butanesulfinimine. Then, the N-tert-butanesulfinyl-protected amine was easily deprotected under acidic conditions. Finally, the primary amine was coupled with different acid chlorides or acids to give the corresponding amides. The mild reaction conditions and high tolerance for various substitutions make this approach attractive for constructing pharmacologically interesting 5-nitroimidazoles.
| S-EPMC6273685 | biostudies-other
Project description:Phosphorus-containing heterocyclic cationic surfactants alkyldimethylphenylphospholium bromides with the alkyl chain length 14 to 18 carbon atoms were used for the stabilization of silver nanodispersions. Zeta potential of silver nanodispersions ranges from +35 to +70 mV, which indicates the formation of stable silver nanoparticles (AgNPs). Long-chain heptadecyl and octadecyl homologs of the surfactants series provided the most intensive stabilizing effect to AgNPs, resulting in high positive zeta potential values and smaller diameter of AgNPs in the range 50-60 nm. A comparison with non-heterocyclic alkyltrimethylphosphonium surfactants of the same alkyl chain length showed better stability and more positive zeta potential values for silver nanodispersions stabilized with heterocyclic phospholium surfactants. Investigations of biological activity of phospholium-capped AgNPs are represented by the studies of antimicrobial activity and cytotoxicity. While cytotoxicity results revealed an increased level of HepG2 cell growth inhibition as compared with the cytotoxicity level of silver-free surfactant solutions, no enhanced antimicrobial action of phospholium-capped AgNPs against microbial pathogens was observed. The comparison of cytotoxicity of AgNPs stabilized with various non-heterocyclic ammonium and phosphonium surfactants shows that AgNPs capped with heterocyclic alkyldimethylphenylphospholium and non-heterocyclic triphenyl-substituted phosphonium surfactants have the highest cytotoxicity among silver nanodispersions stabilized by the series of ammonium and phosphonium surfactants.
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Project description:An uncomplicated, high-yielding synthetic route has been developed to constitute complicated heterocycles, applying domino, click and retro-Diels⁻Alder (RDA) reaction sequences. Starting from 2-aminocarboxamides, a new set of isoindolo[2,1-a]quinazolinones was synthesized with domino ring closure. A click reaction was performed to create the 1,2,3-triazole heterocyclic ring, followed by an RDA reaction resulting in dihydropyrimido[2,1-a]isoindole-2,6-diones. The absolute configuration, concluded by the norbornene structure that served as a chiral source, remained constant throughout the transformations. The structure of the synthesized compounds was examined by ¹H and 13C Nuclear Magnetic Resonance (NMR) methods.
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