- Ultrasound assisted synthesis and cytotoxicity evaluation of known 2′,4′-dihydroxychalcone derivatives against cancer cell lines
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This work reports on the development of an efficient and ecofriendly ultrasound assisted method for the high yield synthesis (70.0–94.0%) of eighteen oxyalkylated derivatives of 2′,4′-dihydroxychalcone. Synthesized compounds were subjected to in vitro biological assays against HT-29 (colorectal), MCF-7 (breast), and PC-3 (prostate) human tumor cell lines, these cell lines are among the ten most aggressive malignancies diagnosed in the world. Cytotoxicity evaluations showed that four of the synthesized compounds exhibited moderate to very high toxic activity against MCF-7 (IC50 = 8.4–34.3 μM) and PC-3 (IC50 = 9.3–29.4 μM) – comparable to 5-fluorouracil (IC50 16.4–22.3 μM). The same compounds only showed moderate activity against HT-29 (IC50 15.3–36.3 μM), closer to daunorubicin (IC50 15.1 μM). Next, although selectivity index (SI) of compounds was weak, compound 18 exhibited a remarkable and selective cytotoxic activity (5.8–10.57) against cancer cells. Outside of these, most compounds significantly reduced cell survival, increased reactive oxygen species (ROS) and caspase activity, and decreased mitochondrial membrane permeability. In this sense, a portion of anti-proliferative activity is due to apoptosis. Notwithstanding, due to its remarkable response, chalcone 18 may be a potential alternative as a chemotherapeutic anti-carcinogen.
- Villena, Joan,Montenegro, Iván,Said, Bastian,Werner, Enrique,Flores, Susana,Madrid, Alejandro
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- Synthesis, molecular docking and α-glucosidase inhibitory activity study of 2,4,6-triaryl pyrimidine derivatives
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Background: α-Glucosidase inhibitors hinder the carbohydrate digestion and play an important role in the treatment of diabetes mellitus. α-glucosidase inhibitors available on the market are acarbose, miglitol, and voglibose. However, the use of acarbose is diminishing due to related side effects like diarrhea, bloating and abdominal distension. Objectives: This study aimed to synthesize 2,4,6-triaryl pyrimidines derivatives, screen their α-glucosidase inhibitory activity, perform kinetic and molecular docking studies. Methods: A series of 2,4,6-triaryl pyrimidine derivatives were synthesized and their α-glucosidase inhibitory activity was screened in vitro. Pyrimidine derivatives 4a-m were synthesized via a two-step reaction with a yield between 49 and 93%. The structure of the synthesized compounds was confirmed by different spectroscopic techniques (IR, NMR and MS). The in vitro α-glucosidase inhibition activities of the synthesized compounds 4a-m was also evaluated against Saccharomyces cerevisiae α-glucosidase. Results and Discussion: The majority of synthesized compounds had α-glucosidase inhibitory activity. Particularly compounds 4b and 4g were the most active compounds with an IC50 value of 125.2± 7.2 and 139.8 ± 8.1 μM respectively. The kinetic study performed for the most active compound 4b revealed that the compound was a competitive inhibitor of Saccharomyces cerevisiae α-glucosidase with Ki of 122 μM. The molecular docking study also revealed that the two compounds have important binding interactions with the enzyme active site. Conclusion: 2,4,6-triarylpyrimidine derivative 4a-m were synthesized and screened for α-glucosidase inhibitory activity. Most of the synthesized compounds possess α-glucosidase inhibitory activity, and compound 4b demonstrated the most significant inhibitory action as compared to acarbose.
- Abdollahi, Mohammad,Amini, Mohsen,Bule, Mohammed Hussen,Esfandyari, Roghaieh,Faramarzi, Mohammad Ali,Tafesse, Tadesse Bekele
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p. 1216 - 1226
(2020/10/06)
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- Design, synthesis, and carbonic anhydrase inhibition activity of benzenesulfonamide-linked novel pyrazoline derivatives
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Carbonic anhydrases (CA, EC 4.2.1.1) are Zinc metalloenzymes and are present throughout most living organisms. Among the catalytically active isoforms are the cytosolic CA I and II, and tumor-associated CA IX and CA XII. The carbonic anhydrase (CA) inhibitory activities of newly synthesized pyrazoline-linked benzenesulfonamides 18–33 against human CA (hCA) isoforms I, II, IX, and XII were measured and compared with that of acetazolamide (AAZ), a standard inhibitor. Potent inhibitory activity against hCA I was exerted by compounds 18–25, with inhibition constant (KI) values of 87.8–244.1 nM, which were greater than that of AAZ (KI, 250.0 nM). Compounds 19, 21, 22, 29, 30, and 32 were proven to have inhibitory activities against hCA IX with KI values (5.5–37.0 nM) that were more effective than or nearly equal to that of AAZ (KI, 25.0 nM). Compounds 20–22, and 30 exerted potent inhibitory activities (KIs, 7.1–10.1 nM) against hCA XII, in comparison with AAZ (KI, 5.7 nM).
- Abdel-Aziz, Alaa A.-M.,El-Azab, Adel S.,Bua, Silvia,Nocentini, Alessio,Abu El-Enin, Mohamed A.,Alanazi, Mohammed M.,AlSaif, Nawaf A.,Hefnawy, Mohamed M.,Supuran, Claudiu T.
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p. 425 - 431
(2019/03/27)
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- QSAR, in silico docking and in vitro evaluation of chalcone derivatives as potential inhibitors for H1N1 virus neuraminidase
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Thirty three chalcones were synthesized and tested on viral H1N1 neuraminidase activity by using MUNANA assay [2′-(4-methylumbelliferyl)-α-d-N-acetylneuraminic acid] assay with DANA (2,3-didehydro-2-deoxy-N-acetylneuraminic acid) was used as standard. 2D and 3D-quantitative structure?activity relationship models have been successfully developed with a good correlative and predictive ability for quantitative structure?activity relationships of these chalcone derivatives. Result from the 2D-quantitative structure?activity relationship model indicates that electrostatic parameter enhanced bioactivity of the chalcones while steric substituents diminished their potency as H1N1 neuraminidase inhibitors. 3D-quantitative structure?activity relationship model showed the importance of the position of the hydroxyl group in chalcone derivatives which can influence on hydrophobicity, hydrogen bond donor and aromatic ring features that enhance the biological activity. Finally, docking studies showed that chalcones MC8 and MC16 with low C docker interaction energies and higher numbers of hydrogen bonding have better inhibitory activity against viral H1N1 neuraminidase.
- Yaeghoobi, Marzieh,Frimayanti, Neni,Chee, Chin Fei,Ikram, Kusaira K.,Najjar, Belal O.,Zain, Sharifuddin M.,Abdullah, Zanariah,Wahab, Habibah A.,Rahman, Noorsaadah Abd.
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p. 2133 - 2142
(2016/10/25)
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- Synthesis, antitubercular activity, and molecular modeling studies of analogues of isoliquiritigenin and liquiritigenin, bioactive components from Glycyrrhiza glabra
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Isoliquiritigenin (ISL, 1) and liquiritigenin (LTG, 2) were isolated from the rhizomes of Glycyrrhiza glabra. In an attempt to develop potent and selective antituberculosis agents, a series of ISL analogues were synthesized mainly via acid- and base-catalyzed Claisen-Schmidt condensation reaction for their antitubercular activity. Compared to ISL (MIC = 25 μg/mL), analogues 5, 8, and 10 showed similar antitubercular activity, but, interestingly, 6, 7, and 15 exhibited twofold higher activity (MIC = 12.5 μg/mL) over ISL, against Mycobacterium tuberculosis. Among the LTG derivatives, LTG 4′-acetate and LTG-oxime were found to be as active (MIC = 25 μg/mL) as LTG. It is the first report on antimycobacterial activity of these ISL- and LTG-based derivatives. Molecular docking and in silico ADME studies revealed that compounds 6, 7, and 15 are potent inhibitors of M. tuberculosis H37Rv alanine dehydrogenase and showed compliance with standard parameters of drug likeness.
- Gaur, Rashmi,Thakur, Jay Prakash,Yadav, Dharmendra K.,Kapkoti, Deepak Singh,Verma, Ram Kishor,Gupta, Namita,Khan, Feroz,Saikia, Dharmendra,Bhakuni, Rajendra Singh
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p. 3494 - 3503
(2015/08/03)
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- In vivo anti-diabetic activity of derivatives of isoliquiritigenin and liquiritigenin
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Isoliquiritigenin (ISL), a chalcone and liquiritigenin (LTG), a flavonoid found in licorice roots and several other plants. ISL displays antioxidant, anti-inflammatory, antitumor and hepatoprotective activities whereas LTG is an estrogenic compound, acts as an agonist selective for the β-subtype of the oestrogen receptor. Both the phenolics were isolated from the rhizomes of Glycyrrhiza glabra. Five derivatives from ISL and four derivatives from LTG were synthesized. All the compounds were established by extensive spectroscopic analyses and screened through oral glucose tolerance test to gain preliminary information regarding the antihyperglycemic effect in normal Swiss albino male mice. ISL (1), ISL derivatives 3, 4, 5, 7 and LTG derivatives 9 and 10 showed significant blood glucose lowering effect. The structure-activity relationship indicated that the presence of ether and ester groups in ISL and LTG analogues are important for exhibiting the activity. Compounds 1, 4 and 10 were selected for in vivo antidiabetic activity and found to be potential candidates for treatment of diabetes. It is the first report on antidiabetic activity of ISL derivative 4 and LTG derivative 10.
- Gaur, Rashmi,Yadav, Kuldeep Singh,Verma, Ram Kishor,Yadav, Narayan Prasad,Bhakuni, Rajendra Singh
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p. 415 - 422
(2014/04/17)
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- NUCLEAR RECEPTOR MODULATORS AND THEIR USE FOR THE TREATMENT AND PREVENTION OF CANCER
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Disclosed are compounds which are nuclear receptor modulators that can act as antagonists to the androgen receptor, for example, a compound of Formula I: wherein R1 to R5 and X1 to X5 are as described herein, as well as pharmaceutically acceptable salts, solvates, and stereoisomers thereof. Pharmaceutical compositions comprising such compounds, as well as methods of use, and treatment for cancers, including prostate cancers, other nuclear receptor mediated cancers, and other conditions, are also disclosed.
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Page/Page column 24
(2013/02/28)
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- Arylalkyl ketones, benzophenones, desoxybenzoins and chalcones inhibit TNF-α induced expression of ICAM-1: Structure-activity analysis
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The interaction between leukocytes and the vascular endothelial cells (EC) via cellular adhesion molecules plays an important role in the pathogenesis of various inflammatory and autoimmune diseases. Small molecules that block these interactions have been targeted as potential therapeutic agents against acute and chronic inflammatory diseases. In an effort to identify potent intercellular cell adhesion molecule-1 (ICAM-1) inhibitors, a large number of arylalkyl ketones, benzophenones, desoxybenzoins and chalcones and their analogs (54 in total) have been synthesized and screened for their ICAM-1 inhibitory activity. The structure-activity relationship studies of these compounds identified three potent chalcone derivatives and also demonstrated the possible mechanism for their ICAM-1 inhibitory activities. The most active compound was found to be 79. A large number of arylalkyl ketones, benzophenones, desoxybenzoins and chalcones as well as their analogs (54 in total) were synthesized and screened for their ICAM-1 inhibitory activity. The structure-activity relationship studies of these compounds identified three potent chalcone derivatives and also demonstrated a possible mechanism of their ICAM-1 inhibitory activities. The most active compound was found to be 79. Copyright
- Kumar, Sarvesh,Reddy L, Chandra Shekhar,Kumar, Yogesh,Kumar, Amit,Singh, Brajendra K.,Kumar, Vineet,Malhotra, Shashwat,Pandey, Mukesh K.,Jain, Rajni,Thimmulappa, Rajesh,Sharma, Sunil K.,Prasad, Ashok K.,Biswal, Shyam,Van Der Eycken, Erik,Depass, Anthony L.,Malhotra, Sanjay V.,Ghosh, Balaram,Parmar, Virinder S.
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experimental part
p. 368 - 377
(2012/07/31)
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- Synthesis and antiinflammatory activity of some new 1,3,5-trisubstituted pyrazolines bearing benzene sulfonamide
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Nineteen new 2-pyrazoline bearing benzenesulfonamide derivatives were synthesized by condensing chalcones with 4-hydrazinonbenzenesulfonamide hydrochloride. Their chemical structures were proved by means of IR, 1H NMR, 13C NMR, mass spectroscopic and elemental analyses data. These compounds were tested at dose of 20 mg/kg for their anti-inflammatory activity in carrageenan-induced rat paw edema model and volume of paw edema was measured at 0, 3 and 5 h. Two compounds 3k and 3l were found to be more active than celecoxib throughout the study (at 3 and 5 h). While two other compounds 3m and 3n showed more potent activity than celecoxib at 5 h. They are devoid of ulcerogenic potential when administered orally at a dose of 60 mg/kg. Compounds (3k-m) showed COX-1 and COX-2 inhibitory activity at 0.05 μM.
- Rathish,Javed, Kalim,Ahmad, Shamim,Bano, Sameena,Alam,Pillai,Singh, Surender,Bagchi, Vivek
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scheme or table
p. 255 - 258
(2009/05/07)
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- α, β-Unsaturated N-Acylureas as Useful Intermediates for the Synthesis of Indanones, Chromanones and Coumarins
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α,β-Unsaturated N-acylureas, viz-N-formamido-2-butenamide (I), N-formamido-3-methyl-2-butenamide (II) and N-formamido-3-phenyl-2-propenamide (III) react with aryl alkyl ethers in the presence of PPA to afford the corresponding crotonophenones and chalcones (IV) at lower temperature and 1-indanones (V) at a higher temperature.Reactions of I and II with phenols in the presence of PPA afford the 4-chromanones (VI), while III gives 3,4-dihydro-4-phenylcoumarins (VII) in excellent yields.
- Ramana, M. M. V.,Kudav, N. A.
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p. 339 - 341
(2007/10/02)
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- Dye-sensitized Photo-oxygenation of Chalcones
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The dye-sensitized photo-oxygenation of several chalcones has been examined.Some of the chalcones give rise to degradation products while others lead to flavonol formation.A rational explanation for the observations has been proposed.The study may have a significance in the biogenesis of naturally occurring plant polyphenolics.
- Chawla, H. Mohindra,Chakrabarty, Kakoli
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p. 1511 - 1513
(2007/10/02)
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