- Identification of 1,2,4-triazoles as new thymidine phosphorylase inhibitors: Future anti-tumor drugs
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Thymidine phosphorylase (TP) is over expressed in several solid tumors and its inhibition can offer unique target suitable for drug discovery in cancer. A series of 1,2,4-triazoles 3a–3l has been synthesized in good yields and subsequently inhibitory potential of synthesized triazoles 3a–3l against thymidine phosphorylase enzyme was evaluated. Out of these twelve analogs five analogues 3b, 3c, 3f, 3l and 3l exhibited a good inhibitory potential against thymidine phosphorylase. Inhibitory potential in term of IC50 values were found in the range of 61.98 ± 0.43 to 273.43 ± 0.96 μM and 7-Deazaxanthine was taken as a standard inhibitor with IC50 = 38.68 ± 4.42 μM. Encouraged by these results, more analogues 1,2,4-triazole-3-mercaptocarboxylic acids 4a–4g were synthesized and their inhibitory potential against thymidine phosphorylase was evaluated. In this series, six analogues 4b–4g exhibited a good inhibitory potential in the range of 43.86 ± 1.11–163.43 ± 2.03 μM. Angiogenic response of 1,2,4-triazole acid 4d was estimated using the chick chorionic allantoic membrane (CAM) assay. In the light of these findings, structure activity relationship and molecular docking studies of selected triazoles to determine the key binding interactions was discussed. Docking studies demonstrate that synthesized analogues interacted with active site residues of thymidine phosphorylase enzyme through π-π stacking, thiolate and hydrogen bonding interactions.
- Shahzad, Sohail Anjum,Yar, Muhammad,Khan, Zulfiqar Ali,Shahzadi, Lubna,Naqvi, Syed Ali Raza,Mahmood, Adeem,Ullah, Sami,Shaikh, Ahson Jabbar,Sherazi, Tauqir Ali,Bale, Adebayo Tajudeen,Kuku?owicz, J?drzej,Bajda, Marek
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p. 209 - 220
(2019/01/10)
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- Design and synthesis of 2,6-di(substituted phenyl)thiazolo[3,2-b]-1,2,4-triazoles as α-glucosidase and α-amylase inhibitors, co-relative Pharmacokinetics and 3D QSAR and risk analysis
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Ten fused heterocyclic derivatives bearing the 2,6-di(subsituted phenyl)thiazolo[3,2-b]-1,2,4-triazoles as central rings were synthesized and structures of the compounds were established by analytical and spectral data using FTIR, EI-MS, 1H NMR and 13C NMR techniques. In vitro inhibitory activities of synthesized compounds on α-amylase, α-glucosidase and α-burylcholinesterase (α-BuChE) were evaluated using a purified enzyme assays. Compound 5c demonstrated strong and selective α-amylase inhibitory activity (IC50?=?1.1?μmol/g). 5?g exhibited excellent inhibition against α-glucosidase (IC50?=?1.2?μmol/g) when compared with acarbose (IC50?=?4.7?μmol/g) as a positive reference. Compound 5i was found to be most potent derivative against α-BuChE with the IC50 of 1.5?μmol/g which was comparable to the value obtained for (4.7?μmol/g) positive control (i.e. galantamine hydrobromide). Molecular dockings of synthesized compounds into the binding sites of human pancreatic α-amylase, intestinal maltase-glucoamylase and neuronal α-butrylcholinesterase allowed to shed light on the affinity and binding mode of these novel inhibitors. Preliminary structure–activity relationship (SAR) studies were carried out to understand the relationship between molecular structural features and inhibition activities of synthesized derivatives. These data suggested that compounds 5c, 5?g and 5i are promising candidates for hitto- lead follow-up in the drug-discovery process for the treatment of Alzheimer's disease and hyperinsulinamia.
- Channar, Pervaiz Ali,Saeed, Aamer,Larik, Fayaz Ali,Rashid, Sajid,Iqbal, Qaiser,Rozi, Maryam,Younis, Saima,Mahar, Jamaluddin
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p. 499 - 513
(2017/08/08)
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- Design, synthesis, and negative inotropic evaluation of 4-phenyl-1H-1,2,4-triazol-5(4H)-one derivatives containing triazole or piperazine moieties
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In this study, four novel series of 4-phenyl-1H-1,2,4-triazol-5(4H)-one derivatives containing triazole or piperazine moieties were designed, synthesized, and evaluated for negative inotropic activity by measuring the left atrium stroke volume in isolated rabbit heart preparations. Almost all of the compounds showed an ability to moderate the cardiac workload by decreasing the heart rate and contractility. Among them, 7h was found to be the most potent with a change in stroke volume of ?48.22?±?0.36% at a concentration of 3?×?10?5?mol/L (metoprolol: ?9.74?±?0.14%). The cytotoxicity of these compounds was evaluated using the human cervical cancer cell line HeLa, the liver cancer cell line Hep3B, and the human normal hepatic cell line LO2. A preliminary study of the mechanism of action for the compound 7h on the regulation of atrial dynamics with ATP-sensitive K+ channel and L-type Ca2+ channel blockers glibenclamide and nifedipine was performed in the isolated perfused beating rabbit atria.
- Wei, Zhi-Yu,Cui, Bai-Ri,Cui, Xun,Wu, Yan-Ling,Fu, Yang,Liu, Li-Ping,Piao, Hu-Ri
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- An efficient nonconventional glycerol-based solid acid catalyzed synthesis and biological evaluation of phosphonate conjugates of 1,2,4-triazole thiones
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A series of diethyl (3-((5-aryl-1H-1,2,4-triazol-3-yl)thio)propyl)phos-phonates (7a-t) has been synthesized in excellent yields by coupling diethyl (3-bromopropyl)phosphonate and 5-aryl-1H- 1,2,4-triazol-3-thiones employing an efficient, green and nonconventional heterogeneous SO3Hcarbon catalyst derived from glycerol. In addition, a facile and green approach for the esterification of carboxylic acids by utilizing glycerol-based solid acid catalyst has been reported. Structures of the synthesized compounds were characterized by IR, NMR and HRMS studies. These triazole derivatives were screened for their in vitro cytotoxicity using the standard MTT (3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetra-zolium bromide) assay against a panel of five different human cancer cell lines (HeLa: Cervix, A549: Lung, A375: Skin, MDA-MB-231: Breast and T98G: Brain). The antimicrobial activities of the synthesized compounds were investigated against four bacterial strains: Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and three fungal strains: Aspergillus Niger, Aspergillus terreus, Aspergillus fumigatus. Preliminary results indicate that the compound 7f displayed maximum anticancer activity and the compounds 7d, 7e, 7f, 7m and 7q exhibited moderate antibacterial activity. The compounds 7g, 7h, 7o and 7p showed good antifungal activity with high inhibition zone diameter compared to the standard drug.
- Murty, Madugula S.R.,Katiki, Mohana R.,Rao, Busam R.,Narayanan, Sai S.,Anto, Ruby J.,Buddana, Sudhreer K.,Prakasham, Reddy S.,Devi, Bethala L.A.P.,Prasad, Rachapudi B.N.
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p. 968 - 981
(2016/10/31)
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- Magnetically Recyclable Nano-Fe 2O 3-Catalyzed Chemoselective Synthesis and Antioxidant Activity of Diethyl (3-((5-Aryl-1 H-1,2,4-triazol-3-yl)thio)propyl) phosphonates
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An efficient, green, and chemoselective S-alkylation of 5-aryl-1H-1,2,4-triazole-3-thiones with diethyl (3-bromopropyl)phosphonate in water, catalyzed by nano-Fe2O3 under ligand-and base-free conditions, is reported. Clean reaction, less expensive catalyst, excellent yields, and easy workup are the advantages of the present method. The catalyst can be easily collected by a magnet and recycled without significant loss in catalytic activity. The newly synthesized compounds were screened for their antioxidant property by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay. The majority of the compounds exhibited good antioxidant activity.
- Murty,Katiki, Mohana Rao,Rao, B. Ramalingeswara,Nanubolu, Jagadeesh Babu,Buddana, Sudheer Kumar,Prakasham
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p. 2724 - 2737
(2014/08/18)
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- Synthesis and antibacterial activities of new S-glycosides bearing 1,2,4-triazole
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Several new 5-aryl-3-(β-D-glucopyranosylthio)-1,2,4-triazoles have been synthesized. The structures of these new compounds were confirmed by 1H NMR, 13C NMR and elemental analyses.The antibacterial activities of the compounds were also evaluated.
- Chao, Shu-Jun,Geng, Ming-Jiang,Wang, Ying-Ling
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scheme or table
p. 731 - 736
(2011/03/21)
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