Synthesis and cytotoxic evaluation of some styryl ketones and related compounds

Dimmock, Jonathan R.; Kumar, Praveen; Quail, J. Wilson; Pugazhenthi, U.; Yang, Jinliang; Chen, M.; Reid, R. S.; Allen, Theresa M.; Kao, G. Y.; Cole, Susan P.C.; Batist, Gerald; Balzarini, Jan; Clercq, Erik De

doi:10.1016/0223-5234(96)88227-4

Cited by 22 publications

(18 citation statements)

References 14 publications

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“…The perceived importance of these compounds is their ability to interact preferentially with thiols in contrast to amino and hydroxyl groups [1,2] which are present in nucleic acids. Thus the genotoxic properties displayed by various alkylating agents in cancer chemotherapy [3] may well be absent in conjugated enones.…”

Section: Introductionmentioning

confidence: 99%

Novel 3,5-bis(arylidene)-4-oxo-1-piperidinyl dimers: Structure–activity relationships and potent antileukemic and antilymphoma cytotoxicity

Santiago-Vazquez

Das

et al. 2014

European Journal of Medicinal Chemistry

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Novel clusters of 3,5-bis(benzylidene)-4-oxo-1-piperidinyl dimers 3–5 were evaluated against human Molt4/C8 and CEM T-lymphocytes and human HeLa cervix adenocarcinoma cells as well as murine L1210 leukemia neoplasms. Several of these compounds demonstrated IC50 values in the submicromolar and low micromolar range and compounds possessing 4-fluoro, 4-chloro and 3,4,5-trimethoxy substituents in the series 3 and 4 were identified as potent molecules. A heat map revealed the very high cytotoxic potencies of representative compounds against a number of additional leukemic and lymphoma cell lines and displayed greater toxicity to these cells than nonmalignant MCF10A and Hs-27 neoplasms. These dienones are more refractory to breast and prostate cancers. The evaluation of representative compounds in series 3–5 against a panel of human cancer cell lines revealed them to be potent cytotoxins with average IC50 values ranging from 0.05 to 8.51 μM In particular, the most potent compound 4g demonstrated over 382-fold and 590-fold greater average cytotoxic potencies in this screen than the reference drugs, melphalan and 5-fluorouracil, respectively. A mode of action investigation of two representative compounds 3f and 4f indicated that they induce apoptosis which is due, at least in part, to the activation of caspase-3 and depolarization of the mitochondrial membrane potential.

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Section: Introductionmentioning

confidence: 99%

Novel 3,5-bis(arylidene)-4-oxo-1-piperidinyl dimers: Structure–activity relationships and potent antileukemic and antilymphoma cytotoxicity

Santiago-Vazquez

Das

et al. 2014

European Journal of Medicinal Chemistry

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“…a,b-Unsaturated ketones alkylate cellular thiols to produce cytotoxicity 20 . It was reported that Mannich bases of styryl ketones have increased cytotoxicity comparing to its styryl ketone analogue 21 . The cytotoxic and anticancer properties of chalcone (1,3-diphenyl-2-propenone) and related compounds have been reported 7,8,15,[22][23][24][25][26][27][28] .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of mono Mannich bases of 2-(4-hydroxybenzylidene)-2,3-dihydroinden-1-one and evaluation of their cytotoxicities

Tuğrak

Yamalı

Sakagami

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Being a thiol alkylator may provide to devoid of the genotoxic properties since thiol groups are not present in nucleic acids 25 . In addition to thiol specificity of a,b-unsaturated ketones, there is a study reporting that Mannich bases of stryryl ketones were free from cross-resistance to several drug resistant cell lines 26 .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of some acrylophenones withN-methylpiperazine and evaluation of their cytotoxicities

Gül

Tuğrak

Sakagami

2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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In this study, the compounds having acrylophenone structure, 1-aryl-2-(N-methylpiperazinomethyl)-2-propen-1-one dihydrochlorides, were synthesized and their chemical structures were identified with 1 H NMR, 13 C NMR and HRMS spectra. The cytotoxicities of the compounds were tested towards Ca9-22 (human gingival carcinoma), HSC-2 (human oral squamous carcinoma), HSC-3 (human oral squamous carcinoma) and HSC-4 (human oral squamous carcinoma) cell lines as tumor cell lines and HGF (gingival fibroblasts), HPLF (periodontal ligament fibroblasts) and HPC (pulp cells) cell lines as non-tumor cell lines. PSE of the compound TA2, which has a methyl substituent on phenyl ring, pointed out the compound TA2 as a leader compound to be considered.

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Synthesis and cytotoxic evaluation of some styryl ketones and related compounds

Cited by 22 publications

References 14 publications

Novel 3,5-bis(arylidene)-4-oxo-1-piperidinyl dimers: Structure–activity relationships and potent antileukemic and antilymphoma cytotoxicity

Novel 3,5-bis(arylidene)-4-oxo-1-piperidinyl dimers: Structure–activity relationships and potent antileukemic and antilymphoma cytotoxicity

Synthesis of mono Mannich bases of 2-(4-hydroxybenzylidene)-2,3-dihydroinden-1-one and evaluation of their cytotoxicities

Synthesis of some acrylophenones withN-methylpiperazine and evaluation of their cytotoxicities

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