- Design, synthesis and biological evaluation of some new 1,3,4-thiadiazine-thiourea derivatives as potential antitumor agents against non-small cell lung cancer cells
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New 1,3,4-thiadiazine-thiourea derivatives have been synthesized. All the synthesized compounds were examined for in vitro cytotoxic activity against Non-Small Cell Lung Cancer (NSCLC) cell line A549, using MTT bioassay. Compounds 5d, 5i, 5j showed the highest cytotoxic activity with IC50 values of 0.27 ± 0.01, 0.30 ± 0.02, and 0.32 ± 0.012 μM respectively with sorafenib as reference (IC50 3.85 ± 0.27 μM). These compounds were chosen for further investigations against various biological targets known to play roles in NSCLC specifically: vascular endothelial growth factor receptor 2 (VEGFR2), B-RAF and matrix metalloproteinase 9 (MMP9). Encouraging results were exhibited by the three compounds against the selected targets. Compound 5j was specially promising as it exhibited inhibitory activity of VEGFR2 close to sorafenib (IC50 0.11 ± 0.01 μM), most potent B-RAF activity inhibition (IC50 0.178 ± 0.004 μM) and MMP9 inhibition (IC50 0.08 ± 0.004 μM). Moreover, cell cycle analysis of A549 cells treated with 5j exhibited cell cycle arrest at G2-M phase and pro-apoptotic activity as indicated by Annexin V-FITC staining. Also, it reflected antinvasive and antimigration properties to A549 cells. Additionally, docking study of 5j on VEGFR2, B-RAF and MMP9 revealed that it binds to the target enzymes in a similar way as the co-crystallized ligand. The three compounds exhibited significantly high selectivity to A549 cancer cells against the normal human fetal lung fibroblast cell line WI-38 with higher selectivity index compared to sorafenib (5d IC50 136.76 ± 2.38 μM, SI = 506.52; 5i IC50 89.20 ± 2.11 μM, SI = 297.33; 5j IC50 79.60 ± 3.8 μM, SI = 248.75; sorafenib IC50 30.32 ± 2.41 μM, SI = 7.88). In conclusion, compounds 5d, 5i and 5j, specially 5j are promising anticancer agents targeting important pathways in NSCLC and warrant further preclinical and clinical trials.
- Ragab, Fatma A.F.,Abdel-Aziz, Salah A.,Kamel, Marwa,Ouf, Abdelsalam Mohamed A.,Allam, Heba Abdelrasheed
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- Synthesis of 2,5-disubstituted 1,3,4-oxadiazine and 1,3,4-thiadiazine from substituted acetophenones and acid hydrazides using [Hydroxyl(tosyloxy)iodo] benzene
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A novel and direct method for the efficient synthesis of 2,5-disubstituted 1,3,4-oxadiazines from the reactions of [hydroxy(tosyloxy)iodo]benzene with substituted acetophenones, followed by the treatment with acid hydrazide and K2CO3, is reported. The met
- Karade, Nandkishor N.,Kondre, Jeevan M.,Gampawar, Sumeet V.,Shinde, Sandeep V.
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experimental part
p. 2279 - 2287
(2009/12/03)
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- Potassium carbonate, a support for the green synthesis of azoles and diazines
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A novel potassium carbonate mediated synthesis of 2-amino-1,3-thia/oxa zoles, 2-amino-1,3,4-thia/oxa diazines and 2-hydrazino-1,3,4-thiadiazines has been described here. The use of K2CO3 allows for an aqueous workup thereby eliminating the organic solvent from both the reaction step and post reaction stage, without compromising the yield and reaction time.
- Kidwai,Venkataramanan,Dave
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p. 1045 - 1047
(2007/10/03)
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- SYNTHESIS AND PROPERTIES OF 1,3,4-THIADIAZINE DERIVATIVES. 1. INVESTIGATION OF THE CONDENSATION OF SUBSTITUTED PHENACYL BROMIDES AND BROMOACETYLPYRIDINES WITH THIOSEMICARBAZIDE
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2-Amino-5-aryl(pyridyl)-6H-1,3,4-thiadiazines and isomeric 2-hydrazino-4-aryl(pyridyl)thiazoles, the ration of which depends on the reaction conditions, were obtained by the reaction of substituted phenacyl bromides and bromoacetylpyridines with thiosemicarbazide.
- Novikova, A. P.,Perova, N. M.,Egorova, L. G.,Bragina, E. I.
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p. 666 - 668
(2007/10/02)
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