14114-45-5Relevant academic research and scientific papers
Design, synthesis, and in silico studies of novel eugenyloxy propanol azole derivatives having potent antinociceptive activity and evaluation of their β-adrenoceptor blocking property
Behrouz, Somayeh,Soltani Rad, Mohammad Navid,Taghavi Shahraki, Bahareh,Fathalipour, Mohammad,Behrouz, Marzieh,Mirkhani, Hossein
, p. 147 - 164 (2019)
The design, synthesis, antinociceptive and β-adrenoceptor blocking activities of several eugenyloxy propanol azole derivatives have been described. In this synthesis, the reaction of eugenol with epichlorohydrin provided adducts 3 and 4 which were N-alkylated by diverse azoles to obtain the eugenyloxy propanol azole analogues in good yields. Adducts 3 and 4 were also reacted with azide ion to obtain the corresponding azide 6. The ‘Click’ Huisgen cycloaddition reaction of 6 with diverse alkynes afforded the title compounds in good yields. The synthesized eugenyloxy propanol azole derivatives were in vivo studied for the acute antinociception on male Spargue Dawley rats using tail-flick test. Compounds 5f, 5g, 7b and 11a exhibited potent analgesic properties in comparison with eugenol as a standard drug. In addition, all compounds were ex vivo tested for β-adrenoceptor blocking properties on isolated left atrium of male rats which exhibited partial antagonist or agonist behaviour compared to the standard drugs. The molecular docking study on the binding site of transient receptor potential vanilloid subtype 1 (TRPV1) has indicated that like capsaicin, eugenyloxy propanol azole analogues exhibited the strong affinity to bind at site of TPRV1 in a “tail-up, head-down” conformation and the presence of triazolyl moieties has played undeniable role in durable binding of these ligands to TRPV1. The in silico pharmacokinetic profile, drug likeness and toxicity predictions carried out for all compounds determined that 5g can be considered as potential antinociceptive drug candidate for future research.
A click chemistry approach for the synthesis of cyclic ureido tethered coumarinyl and 1-aza coumarinyl 1,2,3-triazoles as inhibitors of Mycobacterium tuberculosis H37Rv and their in silico studies
Khanapurmath, Netravati,Kulkarni, Manohar V.,Joshi, Shrinivas D.,Anil Kumar
, (2019)
Nucleoside bases like uracil, pharmacophoric triazoles and benzimidazolones have been used during the present study to design molecular matrices for antitubercular activity, employing Click Chemistry. Click triazoles 4/7/10 have been obtained by the reaction of 4-(Azidomethyl)-2H-chromen-2-ones/quinolin-2(1H)-ones 3 and propargyl ethers 2/6/9 derived from theophylline/6-methyl uracil/2-benzimidazolone respectively. In addition to spectral data structures have been confirmed by single crystal X-ray diffraction studies in case of uracil bis alkyne (6) and theophylline mono triazole (4c). Theophylline linked mono triazoles, 4(a-d) and 6-methyl uracil linked bis triazoles, 7(a-e) have been found to inhibit Mycobacterium tuberculosis H37Rv with MIC values in the range 55.62–115.62 μM. Benzimidazolone bis triazoles, 10(a-n) showed better activity with MIC in the range 2.33–18.34 μM. Molecular modeling studies using Surflex-Dock algorithm supported our results.
Design, synthesis and biological evaluation of theophylline containing variant acetylene derivatives as α-amylase inhibitors
Ruddarraju, Radhakrishnam Raju,Kiran, Gangarapu,Murugulla, Adharvana Chari,Maroju, Ravichandar,Prasad, Devarakonda Krishna,Kumar, Boyina Hemanth,Bakshi, Vasudha,Reddy, Nukala Shravya
, (2019)
A novel pharmacophore with theophylline and acetylene moieties was constructed by using a fragment-based drug design and a series of twenty theophylline containing acetylene conjugates were designed and synthesized, and all the compounds were evaluated by enzyme-based in vitro α-amylase inhibition activity. The in vitro evaluation revealed that most of the compounds displayed good inhibitory activities, and among them nine analogs 13–15, 20, 21 and 24–27 were exhibited more or nearly as equipotent inhibitory activity with IC50 values 1.11 ± 0.07, 1.14 ± 0.17, 1.07 ± 0.01 and 1.21 ± 0.03, 1.33 ± 0.09, 1.17 ± 0.01, 1.05 ± 0.02, 1.61 ± 0.04, 1.02 ± 0.03 μM respectively, as compared with standard, acarbose 1.37 ± 0.26 μM. Further, molecular docking simulation studies were done to identify the interactions and binding mode of synthesized analogs at binding site of α-amylase enzyme (PBD ID: 4GQR). Among the synthesized analogs, two compounds 25 and 27 were selected on the basis of α-amylase inhibition activity and evaluated for in vivo anti-diabetic activity by High Fat Diet-Streptozotocin (HFD-STZ) model in normal rats. At the dose of 10 mg/kg, bw, po these compounds have significantly reduced Plasma Glucose level in rats as compared to pioglitazone. The anti-diabetic activity results showed that the animal treated with the compounds 25 and 27 could better reverse and control the progression of the disease compared to the standard.
Design, synthesis, anticancer, antimicrobial activities and molecular docking studies of theophylline containing acetylenes and theophylline containing 1,2,3-triazoles with variant nucleoside derivatives
Ruddarraju, Radhakrishnam Raju,Murugulla, Adharvana Chari,Kotla, Ravindar,Chandra Babu Tirumalasetty, Muni,Wudayagiri, Rajendra,Donthabakthuni, Shobha,Maroju, Ravichandar,Baburao,Parasa, Lakshmana Swamy
, p. 379 - 396 (2016/08/04)
A new series of theophylline containing acetylene derivatives (6a–6b and 7–13) and theophylline containing 1,2,3-triazoles with variant nucleoside derivatives (20–32) have been designed and synthesized. These compounds were screened for anticancer and antimicrobial activity. Further the computational docking and 2D QSAR were performed using MOE software to identify novel scaffolds. The results showed that compound 29 and 30 exhibit significant cytotoxic effect on all four cancer cells such as lung (A549), colon (HT-29), breast (MCF-7) and melanoma (A375) with IC50values of 2.56, 2.19, 1.89, 4.89?μM and 3.57, 2.90, 2.10, 5.81?μM respectively. Whereas quite different results were observed for these compounds in antimicrobial studies. Compounds 11, 21 and 26 have exhibited significant minimum inhibitory concentrations (MIC) against Staphylococcus aureus, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The docking studies demonstrate that compound 27, 28, 29 and 30 have good dock score and binding affinities with various therapeutic targets in cancer cell proliferation. In addition these compounds have shown acceptable correlation with bioassay results in the regression plots generated in 2D QSAR models. This is the first report to demonstrate the theophylline containing acetylene derivatives and theophylline containing 1,2,3-triazole nucleoside hybrids as potential anticancer and antimicrobial agents with comprehensive in silico analysis.
Click reaction based synthesis, antimicrobial, and cytotoxic activities of new 1,2,3-triazoles
Syed Aly, Mohamed Ramadan El,Saad, Hosam Ali,Mohamed, Mosselhi Abdelnabi Mosselhi
supporting information, p. 2824 - 2830 (2015/06/08)
Three-motif pharmacophoric models 20a-e and 21-25 were prepared in good yields by CuAAC of two azido substrates 2 and 11 with seven terminal acetylenic derivatives including chalcones 17a-e, theophylline 18 and cholesterol 19. The structure of these compounds was elucidated by NMR, MS, IR spectroscopy and micro analyses. This series was screened as antimicrobial and cytotoxic agents in vitro. Most derivatives showed appreciable antibacterial activity, but they displayed weak cytotoxic, and antifungal activities. Notably, conjugate 25 (cream of the crop) was found to be more active than Ampicillin against Escherichia coli and Staphylococcus aureus and showed appreciable antifungal and cytotoxic activities as well.
Copper/graphene/clay nanohybrid: A highly efficient heterogeneous nanocatalyst for the synthesis of novel 1,2,3-triazolyl carboacyclic nucleosides via 'Click' Huisgen 1,3-dipolar cycloaddition
Navid Soltani Rad, Mohammad,Behrouz, Somayeh,Jafar Hoseini,Nasrabadi, Hasan,Saberi Zare, Maryam
, p. 1210 - 1224 (2015/09/28)
A very mild and highly efficient synthesis of some novel 1H-1,2,3-triazolyl carboacyclic nucleosides via a 'Click' Huisgen cycloaddition of N-propargyl nucleobases and azido alcohols using Cu/aminoclay/reduced graphene oxide nanohybrid (Cu/AC/r-GO nanohybrid) as nanocatalyst is described. The preparation and characterization of Cu/AC/r-GO nanohybrid are discussed. This catalyst was characterized by X-ray diffraction, FT-IR, TEM, and energy-dispersive analysis of X-ray techniques. Cu/AC/r-GO nanohybrid is a stable and highly efficient heterogeneous nanocatalyst that can be easily prepared, used, and restored from the reaction mixture by simple filtration, and reused for many consecutive trials without significant decrease in activity.
Synthesis and characterization of theophylline-triazole and theophylline-triazole-coumarin based molecular hybrids
Joshi, Penny,Rawata, Diwan S.
, p. 411 - 418 (2019/01/21)
A series of novel theophylline-triazole and theophylline-coumarin conjugates linked via triazole moiety employing click chemistry has been synthesized and characterized by FT-IR, 1H and 13C NMR, and mass-spectral methods. The reaction was performed regioselectively by using copper sulfate and sodium ascorbate to give 1,2,3-triazoles through Cu(I)-catalyzed azide- alkyne cycloaddition.
1,4-Dihydroxyanthraquinone-copper(II) nanoparticles immobilized on silica gel: A highly efficient, copper scavenger and recyclable heterogeneous nanocatalyst for a click approach to the three-component synthesis of 1,2,3-triazole derivatives in water
Sharghi, Hashem,Khoshnood, Abbas,Doroodmand, Mohammad Mahdi,Khalifeh, Reza
experimental part, p. 231 - 250 (2012/09/11)
High yielding preparation of structurally different β-hydroxy 1,4-disubstituted 1,2,3-triazole from the regio-selective reaction of epoxides 2a-2c with wide range of terminal alkynes 1a-1j, and sodium azide in the presence of catalytic amount, complexed form of homogeneous catalyst [bis 1,4-mono ester hydroxy anthraquinone copper(II)] (5.0 mol%), [AQ 2Cu(II)] 7 at 25 °C in water has been described. To benefit from the recovery and reuse of the catalyst, a novel heterogeneous nanoparticles of catalyst [bis 1,4-mono ester hydroxy anthraquinone copper(II) aminopropyl silica gel] (5.0 mol%), [AQ2Cu(II)-APSiO2] 13 bearing oxygen anthraquinone ligands with strong copper(II) affinity was easily prepared by using silica gel as a suitable support. The heterogeneous catalyst was fully characterized by XRD, SEM, AFM, ICP, TG methods for analysis of nitrogen adsorption, and FT-IR techniques. The remarkable features of this protocol are high yields, short reaction times, a cleaner reaction profile in an environmentally benign solvent (H2O), one-pot procedure and the method is applicable to large-scale operation without any problem. Furthermore, the catalyst could be recovered and easily removed by simple filtration of the reaction mixture and it was recycled ten times showing negligible copper leaching. In their uncomplexed form of homogeneous catalyst [AQ 2Cu(II)] 7 and heterogeneous catalyst [AQ2Cu(II)- APSiO2] 13, the anthraquinone ligand 6 and [AQ-APSiO2] 12 are very efficient copper scavengers able to catalyze the 1,3-dipolar cycloaddition reaction of azides with alkynes (CuAAC) without pre-synthesis of catalysts.
'Click synthesis' of 1H-1,2,3-triazolyl-based oxiconazole (=(1Z)-1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethanone O-[(2,4- dichlorophenyl)methyl]oxime) analogs
Soltani Rad, Mohammad Navid,Asrari, Zeinab,Behrouz, Somayeh,Hakimelahi, Gholam Hossein,Khalafi-Nezhad, Ali
experimental part, p. 2194 - 2206 (2012/01/31)
The 'click synthesis' of some oxiconazole analogs 5a-5v having 1H-1,2,3-triazolyl residues by Huisgen cycloaddition was achieved in four steps (Scheme 1). Oximation of phenacyl chloride (1) followed by azidation of 2-chloro-1-phenylethanone oxime (2) provided azido ketoxime 3. The CuI-catalyzed Huisgen cycloaddition of 3 with terminal alkynes gave the 4-substituted (at the triazole) 2-(1H-1,2,3-triazol-1-yl)-1-phenylethanone oximes 4a-4i. The O-alkylation of 4a-4i with various alkyl halides resulted in the formation of the target molecules 5a-5v in good yields. Copyright
Analogue of Coffeine and Theophylline: Effect of Structural Alterations on Affinity at Adenosine Receptors
Daly, J. W.,Padgett, W. L.,Shamim, M. T.
, p. 1305 - 1308 (2007/10/02)
A variety of analogues of caffeine and theophylline in which the 1-, 3-, and 7-methyl substituents have been replaced with n-propyl, allyl, propargyl, and isobutyl and, in few cases with chloroethyl, hydroxyethyl, or benzyl were assessed for potency and s
