Synthesis of Novel Fused Regioisomeric Oxetane Bicycles via Paternò-Büchi Reaction of L-Ascorbic Acid and Evaluation as Antiproliferative Agents

Aim and Objective: To develop efficient method for the synthesis of unusual oxetanes bicycle and diversely functionalized oxetane motifs bearing medicinally relevant functional group in new chemical space and evaluation as cytotoxic agents. Materials and Methods: General procedure for the synthesis of 2, 3, 9 and 11: A mixture of L-ascorbic acid derivative 1 or 8 or 10 (10 mmol) and benzophenone (12 mmol) in dry benzene (125 mL) was purged with dry nitrogen for 5 min. The solution was then irradiated for 20-24 h with UV light (125 W, medium-pressure mercury lamp) in an immersion-well photoreactor at ambient temperature under nitrogen. After completion of the reaction, the solution was washed with aqueous NaHCO3 (10%), dried (Na2SO4), and concentrated under reduced pressure to give crude product which was purified by column chromatography using ethyl acetate: n-hexane (5-20%) as eluent to yield pure product as white solid. Results: 3-O and 2-O methyl derivatives of 5,6-O-isopropylidene-L-ascorbic acid 8 and 10 were irradiated with Benzophenone to give single regioisomer 9 and 11 in 78 % and 69 % yield respectively, while in case of 5,6-O-isopropylidene-2,3-di-O-methyl-L-ascorbic acid, it gave both regioisomer 2 and 3. The presence of only oxetanes moiety improved the cytotoxic activity compared to oxetanes bicycle moiety. It was scrutinized that all the compounds in series of 2 and 4 displayed more MCF-7 cell proliferation than their regioisomers 3 and 6. Conclusion: We have developed a versatile strategy to prepare diversely functionalized fused oxetane bicycles involving alkoxy, hydroxy methyl, alkyl, and aryl substituents. A wide variety of functional groups have been introduced on the oxetane ring, accessing new chemical space. These compounds were tested for growth inhibition against MCF-7 breast cancer cell line, compounds 2d, 4b, 4d and 6d showed comparable cytotoxic activity with L-ascorbic acid. These oxetane motifs will provide interesting new structural elements for medicinal chemistry programs as well as synthesis.

Download Full-text

Design, Synthesis and Cytotoxicity Evaluation of New 3, 5-Disubstituted-2-Thioxoimidazolidinones

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666171129213838 ◽

2018 ◽

Vol 18 (4) ◽

pp. 573-582 ◽

Cited By ~ 1

Author(s):

Khaled R.A. Abdellatif ◽

Mostafa M. Elbadawi ◽

Mohammed T. Elsaady ◽

Amer A. Abd El-Hafeez ◽

Takashi Fujimura ◽

...

Keyword(s):

Breast Cancer ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Topoisomerase I ◽

Cancer Cell Line ◽

Cytotoxic Agents ◽

Dependent Manner ◽

Human Lung Fibroblast ◽

Mcf 7

Background: Some 2-thioxoimidazolidinones have been reported as anti-prostate and anti-breast cancer agents through their inhibitory activity on topoisomerase I that is considered as a potential chemotherapeutic target. Objective: A new series of 3,5-disubstituted-2-thioxoimidazolidinone derivatives 10a-f and their S-methyl analogs 11a-f were designed, synthesized and evaluated for cytotoxicity against human prostate cancer cell line (PC-3), human breast cancer cell line (MCF-7) and non-cancerous human lung fibroblast cell line (WI-38). </P><P> Results and Method: While compounds 10a-f showed a broad range of activities against PC-3 and MCF-7 cell lines (IC50 = 34.0 – 186.9 and 24.6 – 147.5 µM respectively), the S-methyl analogs 11a-f showed (IC50 = 22.7 – 198.5 and 16.9 – 188.2 µM respectively) in comparison with 5-fluorouracil (IC50 = 60.7 and 40.7 µM respectively). 11c (IC50 = 22.7 and 29.2 µM) and 11f (IC50 = 28.7 and 16.9 µM) were the most potent among all compounds against both PC-3 and MCF-7 respectively with no cytotoxicity against WI-38. Conclusion: The newly synthesized compounds showed good activity against PC-3 and MCF-7 cell lines in comparison with 5-fluorouracil. Compounds 11c and 11f bound with human topoisomerase I similar to its known inhibitors and significantly inhibited its DNA relaxation activity in a dose dependent manner which may rationalize their molecular mechanism as cytotoxic agents.

Download Full-text

Design, Syntheses, and Bioevaluations of Some Novel N2-Acryloylbenzohydrazides as Chemostimulants and Cytotoxic Agents

Medicines ◽

10.3390/medicines8060027 ◽

2021 ◽

Vol 8 (6) ◽

pp. 27

Author(s):

Kinjal Lakhani ◽

Edgar A. Borrego ◽

Karla G. Cano ◽

Jonathan R. Dimmock ◽

Renato J. Aguilera ◽

...

Keyword(s):

Antineoplastic Agent ◽

Cytotoxic Agents ◽

Breast Cancer Cell Lines ◽

Molecular Features ◽

In Series ◽

Hct 116 ◽

Related Series ◽

Hct 116 Cells ◽

Related Compounds ◽

Mcf 7

A series of novel N2-acryloylhydrazides 1a–m and a related series of compounds 6a–c were prepared as potential chemostimulants. In general, these compounds are cytotoxic to human HCT 116 colon cancer cells, as well as human MCF-7 and MDA-MB-231 breast cancer cell lines. A representative compound N1-(3,4-dimethoxyphenylcarbonyl)-N2-acryloylhydrazine 1m sensitized HCT 116 cells to the potent antineoplastic agent 3,5-bis(benzylidene)-4-piperidone 2a, and also to 5-fluorouracil. A series of compounds was prepared that incorporated some of the molecular features of 2a and related compounds with various N2-acryloylhydrazides in series 1. These compounds are potent cytotoxins. Two modes of action of representative compounds are the lowering of mitochondrial membrane potential and increasing the concentration of reactive oxygen species.

Download Full-text

Synthesis and cytotoxic activity of certain benzothiazole derivatives against human MCF-7 cancer cell line

Chemical Biology & Drug Design ◽

10.1111/cbdd.12879 ◽

2016 ◽

Vol 89 (4) ◽

pp. 566-576 ◽

Cited By ~ 5

Author(s):

Lamia W. Mohamed ◽

Azza T. Taher ◽

Ghada S. Rady ◽

Mamdouh M. Ali ◽

Abeer E. Mahmoud

Keyword(s):

Cytotoxic Activity ◽

Cell Line ◽

Cancer Cell ◽

Cancer Cell Line ◽

Benzothiazole Derivatives ◽

Mcf 7

Download Full-text

Cytotoxic Activity of Compounds from Styrax obassia

Natural Product Communications ◽

10.1177/1934578x1701200230 ◽

2017 ◽

Vol 12 (2) ◽

pp. 1934578X1701200 ◽

Cited By ~ 1

Author(s):

Thao Quyen Cao ◽

Bo Mi Lee ◽

Yeon Woo Jung ◽

Van Thu Nguyen ◽

Jeong Ah Kim ◽

...

Keyword(s):

Cytotoxic Activity ◽

Cell Line ◽

Cancer Cell ◽

Leukemia Cell ◽

Cancer Cell Line ◽

Stem Bark ◽

Leukemia Cell Line ◽

Cervical Cancer Cell Line ◽

Cell Line Hela ◽

Mcf 7

Cancer is a major public health burden in both developed and developing countries. Plant-derived compounds have played an important role in the development of useful anti-cancer agents. The current study was designed to evaluate the cytotoxic activity of chemical compounds from the stem bark of Styrax obassia. Seven known compounds (1–7) were isolated and identified. Compound 2 exhibited cytotoxic activity against the breast cancer cell line MCF-7 with an IC50 of 27.9 μM, followed by the human cervical cancer cell line Hela with an IC50 of 23.3 μM, and the human promyelocytic leukemia cell line HL-60 with an IC50 of 47.8 μM. Compound 7 exhibited cytotoxicity against Hela cells with an IC50 of 16.8 μM, followed by MCF-7 cells with an IC50 of 53.5 μM. This is the first study to investigate the significant anti-tumor properties of isolated compounds from the stem bark of S. obassia.

Download Full-text

Design, Synthesis, Characterization and Computational Evaluation of Novel Isobutychalcones as Cytotoxic Agents: Part-A

10.20944/preprints201611.0043.v1 ◽

2016 ◽

Author(s):

Afzal Basha Shaik ◽

Yejella Rajendra Prasad ◽

Shaik Shahanaaz

Keyword(s):

Cytotoxic Activity ◽

Aromatic Ring ◽

Cell Lines ◽

Pharmacophore Model ◽

Analysis Data ◽

Structural Features ◽

Cytotoxic Agents ◽

Elemental Analysis Data ◽

Ht 29 ◽

Mcf 7

A series of novel isobutylchalcones (A1-A20) were prepared, evaluated for their cytotoxic activity and characterized by FTIR, 1H NMR, 13C NMR, and elemental analysis data. The logic behind the design is to synthesize and compare chalcones containing electron releasing lipophilic isobutyl substituent on aromatic ring A and the B ring with aromatic ring containing a range of electron releasing and electron withdrawing groups as well as heteroaromatic rings for their cytotoxic activity. The compounds were tested against HT-29 (colon cancer), MCF-7 (breast cancer) and DU-145 (prostate cancer) cell lines using methotrexate (IC50 12 ± 1 (HT-29), 9 ±1 (MCF-7) 5 ± 1 (DU-145)) as reference standard. Compound A6 having 2,4-difluorphenyl moiety was most potent of the series against all the three cell lines and notably A6 was mainly effective against DU-145 cell lines with an IC50 value of 18 µg/mL. The critical structural features required for the activity against all the cell lines were identified through pharmacophore model using PHASETM which has recognised a 5 point AHHRR model and is consistent with the cytotoxic activity of the tested compounds.

Download Full-text

CYTOTOXIC ACTIVITY AND SELECTIVITY INDEX OF BINAHONG (Anredera cordifolia) EXTRACTS ON MCF-7 BREAST CANCER CELLS AND VERO NORMAL CELLS LINE

Acta Biochimica Indonesiana ◽

10.32889/actabioina.v3i2.57 ◽

2021 ◽

Vol 3 (2) ◽

pp. 72-80

Author(s):

Dita Sozianty ◽

Rifki Febriansah

Keyword(s):

Breast Cancer ◽

Cytotoxic Activity ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Selectivity Index ◽

Cytotoxic Agents ◽

Flavonoid Compounds ◽

Ic50 Value ◽

Her 2 ◽

Mcf 7

Background: Breast cancers occur because of an impaired balance between proliferation, differentiation, and apoptosis of breast glands. Natural products have potency as cytotoxic agents with less side effects than chemotherapy. One of the potential plants is Anredera cordifolia (Ten.) Stennis (binahong), which contains flavonoid 8-glucopyranosyl- 4’,5,7-trihydroxy flavone compounds.Objective: This study aims to determine the potency of binahong leaves extract as an anticancer for breast cancer in vitro and in silico.Methods: Preliminary tests using molecular docking of 8-glucopyranosyl-4’,5,7-trihydroxyflavone compounds on Bcl-2 and HER-2 proteins. The extraction and fractionation were to obtain binahong extract. Thin layer chromatography to identify flavonoid compounds in the extract. DPPH assay was performed to evaluate the antioxidant activity. MTT assay was performed to evaluate cytotoxic activity on MCF-7 breast cancer cells and Vero cells.Results: In silico test showed a stable bond between 8-glucopyranosyl- 4’,5,7-trihydroxylflavone, and Bcl-2 and HER-2 with a docking score of -7.5 kcal/mol and -8.0 kcal/mol, respectively. The binahong extract contain flavonoid compounds that had the retention factor value 0.78; 0.49; 0.35. Antioxidant test resulted IC50 value of 4940 μg/mL. Cytotoxic test resulted in IC50 value of 1073 μg/mL and 486 μg/mL for Vero cells and MCF-7 breast cancer cells, respectively. The comparison between IC50 produced a selectivity index value of 2.149, which shows that binahong extract was selective against MCF-7 breast cancers.Conclusion: This study concluded that binahong extract has weak potency as anticancer agent on MCF-7 cells.

Download Full-text

Encapsulation of Variabilin in Stearic Acid Solid Lipid Nanoparticles Enhances Its Anticancer Activity in Vitro

Molecules ◽

10.3390/molecules25040830 ◽

2020 ◽

Vol 25 (4) ◽

pp. 830

Author(s):

Mookho S. Lerata ◽

Sarah D’Souza ◽

Nicole R.S. Sibuyi ◽

Admire Dube ◽

Mervin Meyer ◽

...

Keyword(s):

Natural Products ◽

Cytotoxic Activity ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Line ◽

Lipid Nanoparticles ◽

Structural Assignment ◽

Ic50 Values ◽

Ht 29 ◽

Mcf 7

The use of natural products as chemotherapeutic agents is well established; however, many of these are associated with undesirable side effects, including high toxicity and instability. Furthermore, the development of drug resistant cancers makes the search for new anticancer lead compounds a priority. In this study, the extraction of an Ircinia sp. sponge resulted in the isolation of an inseparable mixture of (7E,12E,20Z)-variabilin (1) and (7E,12Z,20Z)-variabilin (2) and structural assignment was established using standard 1D and 2D NMR experiments. The cytotoxic activity of the compound against three solid tumour cell lines displayed moderate anti-cancer activity through apoptosis, together with a general lack of selectivity among the cancer cell lines studied. Structural assignment and cytotoxic evaluation of variabilin was complicated and further aggravated by its inherent instability. Variabilin was therefore incorporated into solid lipid nanoparticles (SLNs) and the stability and cytotoxic activity evaluated. Encapsulation of variabilin into SLNs led to a marked improvement in stability of the natural product coupled with enhanced cytotoxic activity, particularly against the prostate (PC-3) cancer cell line, with IC50 values of 87.74 μM vs. 8.94 μM for the variabilin alone and Var-SLN, respectively. Both variabilin and Var-SLN revealed comparable activity to Ceramide against the MCF-7 breast cancer cell line, revealing IC50 values of 34.8, 38.1 and 33.6 μM for variabilin, Var-SLN and Ceramide, respectively. These samples revealed no activity (>100 μM for all) against HT-29 (colon) cell lines and MCF-12 (normal breast) cell lines. Var-SLNs induced 47, 48 and 59% of apoptosis in HT-29, MCF-7 and PC-3 cells, respectively, while variabilin alone revealed 38, 29 and 29% apoptotic cells for HT-29, MCF-7 and PC-3 cell lines, respectively. The encapsulation of natural products into SLNs may provide a promising approach to overcome some of the issues hindering the development of new anticancer drugs from natural products.

Download Full-text