Discovery of a series of 1,3,4-oxadiazole-2(3 H )-thione derivatives containing piperazine skeleton as potential FAK inhibitors

Sun, Juan; Ren, Shen-Zhen; Lü, Xiaoyuan; Li, Jingjing; Shen, Fa-Qian; Xu, Chen; Zhu, Hai‐Liang

doi:10.1016/j.bmc.2017.03.038

Cited by 48 publications

(27 citation statements)

References 25 publications

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“…The influence of compound 13 on tyrosine kinase activity was also studied. Among all the derivatives obtained, it showed the highest FAK inhibitory activity [29].…”

Section: Anti-proliferative Effects Of 134-oxadiazole Derivativesmentioning

confidence: 99%

Anti-Cancer Activity of Derivatives of 1,3,4-Oxadiazole

2018

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Compounds containing 1,3,4-oxadiazole ring in their structure are characterised by multidirectional biological activity. Their anti-proliferative effects associated with various mechanisms, such as inhibition of growth factors, enzymes, kinases and others, deserve attention. The activity of these compounds was tested on cell lines of various cancers. In most publications, the most active derivatives of 1,3,4-oxadiazole exceeded the effect of reference drugs, so they may become the main new anti-cancer drugs in the future.

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“…The influence of compound 13 on tyrosine kinase activity was also studied. Among all the derivatives obtained, it showed the highest FAK inhibitory activity [29].…”

Section: Anti-proliferative Effects Of 134-oxadiazole Derivativesmentioning

confidence: 99%

Anti-Cancer Activity of Derivatives of 1,3,4-Oxadiazole

2018

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“…FAK plays an important role in regulating cellular adhesion, motility proliferation, and survival . It also plays an important role in cancer cells survival, invasion, angiogenesis, and metastasis . FAK is overly expressed in ovarian, breast, pancreatic, and colorectal cancer …”

Section: Resultsmentioning

confidence: 99%

“…31 It also plays an important role in cancer cells survival, invasion, angiogenesis, and metastasis. 32 FAK is overly expressed in ovarian, breast, pancreatic, and colorectal cancer. 31,33 Based on the previous predicted target, a docking study was performed to confirm the affinity of compound 1 and 2 to the predicted target computationally.…”

Section: Target Prediction and Docking Studymentioning

confidence: 99%

Radioiodination and biological distribution of a new s‐triazine derivative for tumor uptake evaluation

Motaleb

Ibrahim

Sarhan

et al. 2018

Labelled Comp Radiopharmac

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A newly synthesized s-triazine derivative 1,1',1″-(((1,3,5-triazine-2,4,6-triyl) tris (azanediyl)) tris (benzene-4,1-diyl))tris (ethan-1-one), (1), was synthesized as a part of an ongoing research for development of novel s-triazine-based radiopharmaceuticals. In-vitro cell viability assay against different human cancer cell lines showed very promising inhibitory activity of the synthesized compound. This finding encouraged the radioiodination of 1 to study the degree of its localization in tumor site for evaluating the possibility of its use as a tumor imaging agent. The biodistribution study showed good localization of the radioiodinated derivative 2 at tumor site following i.v. administration in solid tumor-bearing mice. Finally, in a trial to understand the mechanism of the anticancer effect exerted by 1, a target prediction study and a docking study were performed. The results of the first study showed that focal adhesion kinase is a possible target for compound 1 and the docking study confirmed successful binding of both compound 1 and its radioiodinated derivative 2 to the binding site of focal adhesion kinase. As a conclusion, the results of this study suggest that, compound 2 could be used as a potential agent for tumor imaging after preclinical trials.

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“…The ascending order of anticancer activity of compounds 6h, 6j and 6e was due to the different substituted alkyl groups at aromatic ring of propanamides. Compound 6h, 6j both have aromatic ring of propanmides substituted with bulky ethyl groups which might be responsible for their lower anticancer activity when compared to compound 6e having substitution of methyl group at ortho position of aromatic ring [19,20].…”

Section: Discussionmentioning

confidence: 99%

“…Verification of numbers of carbon atoms were done by the help of 13 C-NMR spectrum. Four methyl groups and eight quaternary carbons were appeared at 21.08(C-7''),19.48 (C-3''''), 17.48 (C-7'''), 21.48 (C-8'''), and170.9 (C-1''''), 163.7 (C-5), 163.1 (C-2), 145.39 (C-4''), 137.68 (C-1''), 137.25 (C-1'''), 134.52 (C-5'''), 131.69 (C-2''') respectively.Aromatic carbons were verified by the peaks at 130.90 (C-3'' & C-5''), 128.86 (C-2'' & C-6''), 129.20 (C-4'''), 126.66 (C-3'''), 123.76 (C-6''') while the signal for carbons of piperidine ring and carbonyl group were appeared at 46.53 (C-2' & C-6'), 33.45 (C-4'), 29.65 (C-3' & C-5') and 170.8 (C-1''''). -NMR spectrum presented doublets as 7.69 (d, J = 9.2 Hz, 2H, H-2'' & H-6''), 7.46 (d, J = 9.5 Hz, 2H, H-3'' & H-5'') for 4methylbenzenesulfonyl group and one singlet and two doublets at of aromatic ring of amide group at 7.42 (s, 1H, H-6'''), 7.11 (d, J = 7.8 Hz, 1H, H-3'''), 6.93 (d, J = 8.5 Hz, 1H, H-4''').…”

mentioning

confidence: 99%

Synthesis of some new propanamide derivatives bearing 4- piperidinyl-1,3,4-oxadiazole, and their evaluation as promising anticancer agents

Rehman¹,

Ahtzaz²,

Abbasi³

et al. 2018

Trop. J. Pharm Res

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Purpose: To sequentially synthesize piperidine-4-carboxylic acid ethyl ester-appended 1,3,4-oxadiazole hybrids and to evaluate them as anticancer agents. Methods: Ethyl 1-[(4-methylphenyl)sulfonyl]-4-piperidinecarboxylate (1) was synthesized from 4methylbenzenesulfonylchloride (a) and ethyl 4-piperidinecarboxylate (b). Compound (1) was converted into ethyl 1-[(4-methylphenyl)sulfonyl]-4-piperidine carbohydrazides (2) and 5-{1-[(4methylphenyl)sulfonyl]-4-piperidinyl}-1,3,4-oxadiazole-2-thiol (3) respectively. A variety of aryl amine (4a-l) were treated with 2-bromopropionylbromide to synthesize an array of propanamide (5a-l). Finally, 5-{1-[(4-methylphenyl)sulfonyl]-4-piperidinyl}-1,3,4-oxadiazole-2-thiol (3) and propanamides (5a-l) were reacted to synthesize target compounds (6a-l). Purity compounds 6a-l was confirmed by spectroscopic techniques like (1 H-NMR), (13 C-NMR) and EI-MS. To determine their anticancer potential, the change in absorbance of mixture and cell line before and after incubation was determined. Results: All the compounds 6a-l were successfully synthesized in 73-85 % yield. Compounds 6h, 6j and 6e have low IC50 (±SD) values of 20.12 ± 6.20, 10.84 ± 4.2 and 24.57 ± 1.62 µM to act as strong anticancer agents relative to doxorubicin (0.92 ± 0.1 µM) used as a reference. Conclusion: The synthesized propanamide derivatives bearing 4-piperidinyl-1,3,4-oxadiazole are potential anticancer agents, but further studies, especially in vivo, are required to ascertain their therapeutic usefulness.

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Discovery of a series of 1,3,4-oxadiazole-2(3 H )-thione derivatives containing piperazine skeleton as potential FAK inhibitors

Cited by 48 publications

References 25 publications

Anti-Cancer Activity of Derivatives of 1,3,4-Oxadiazole

Anti-Cancer Activity of Derivatives of 1,3,4-Oxadiazole

Radioiodination and biological distribution of a new s‐triazine derivative for tumor uptake evaluation

Synthesis of some new propanamide derivatives bearing 4- piperidinyl-1,3,4-oxadiazole, and their evaluation as promising anticancer agents

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