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

Medicines ◽  
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.

scholarly journals CYTOTOXIC LABDANE DITERPENOIDS FROM ANDROGRAPHIS PANICULATA (BURM.F.) NEES

2017 ◽  
Vol 10 (12) ◽  
pp. 99 ◽  
Author(s):  
Maria Carmens Tan ◽  
Glenn G Oyong ◽  
Chien Chang Shen ◽  
Consolacion Y Ragasa
Keyword(s):  
Dermal Fibroblasts ◽  
Multiple Comparison ◽  
Wild Type ◽  
Significant Difference ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Labdane Diterpenoids ◽  
Post Hoc ◽  
Ht 29 ◽  
Mcf 7

Objective: The primary objective of this study was to probe the cytotoxic capacity of the labdane diterpenoids andrographolide (1), 14-deoxyandrographolide (2), 14-deoxy-12-hydroxyandrographolide (3), and neoandrographolide (4) on mutant and wild-type immortalized cell lines.Methods: Breast adenocarcinoma (MCF-7), colon carcinomas (HCT-116 and HT-29), small cell lung carcinoma (H69PR), human acute monocytic leukemia (THP-1), and wild-type primary normal human dermal fibroblasts - neonatal cells (HDFn) were incubated with 1-4, and the degree of cytotoxicity was analyzed by employing the in vitro PrestoBlue® cell viability assay. Working solutions of 1-4 were prepared in complete cell culture medium to a final non-toxic dimethyl sulfoxide concentration of 0.2%. The plates were incubated at 37°C with 5% CO2 in a 98% humidified incubator throughout the assay. Nonlinear regression and statistical analyses were done to extrapolate the half maximal inhibitory concentration 50% (IC50). One-way ANOVA (p<0.05) and multiple comparison, Tukey’s post hoc test (p<0.05), were used to compare different pairs of data sets. Results were considered statistically significant at p<0.05.Results: The highest cytotoxicity index was exhibited by the H69PR and 1 trials which displayed the lowest IC50 value of 3.66 μg/mL, followed by HT-29 treated with 2, HCT-116 and 1 trials, and H69PR treated with 4 (IC50=3.81, 3.82, and 4.19 μg/mL, respectively). Only 1 and 4 were detrimental toward MCF-7, while 1, 3, and 4 were degenerative against H69PR. Tukey’s post hoc multiple comparison indicated no significant difference in the cytotoxicity of 1-4 on HCT-116 cells which afforded IC50 values ranging from 3.82 to 5.12 μg/mL. Evaluation of the two colon carcinoma cell lines showed that HCT-116 was categorically more susceptible to cellular damage caused by treatments with 1-4 than was HT-29. Cytotoxicity was not detected in THP-1 and HDFn cells (IC50>100 μg/mL).Conclusion: Diterpenoids 1-4 isolated from the dichloromethane extract of the leaves of A. paniculata exhibited different cytotoxic activities against MCF-7, HCT-116, HT-29, and H69PR. All constituents had comparable action on HCT-116 cells but were not found to be cytotoxic to normal HDFn cells and mutant THP-1 cells.

Immunological evaluation of the entirely carbohydrate-based Thomsen-Friedenreich – PS B conjugate

2016 ◽  
Vol 14 (13) ◽  
pp. 3350-3355 ◽  
Author(s):  
Kevin R. Trabbic ◽  
Jean-Paul Bourgault ◽  
Mengchao Shi ◽  
Matthew Clark ◽  
Peter R. Andreana
Keyword(s):  
T Cell ◽  
Tumor Antigen ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Immunological Evaluation ◽  
Mcf 7 ◽  
Zwitterionic Polysaccharide

PS B, a CD4+T-cell stimulating zwitterionic polysaccharide fromB. fragilis, was conjugated with aminooxy TF tumor antigen. Immunization revealed Ab specificity to TF. FACS revealed Ab binding to MCF-7 but not HCT-116 cells.

scholarly journals Anti-Proliferation Effects of Benzimidazole Derivatives on HCT-116 Colon Cancer and MCF-7 Breast Cancer Cell Lines

2012 ◽  
Vol 13 (8) ◽  
pp. 4075-4079 ◽  
Author(s):  
Mohammed Hadi Al-Douh ◽  
Hayder B. Sahib ◽  
Hasnah Osman ◽  
Shafida Abd Hamid ◽  
Salizawati M. Salhimi
Keyword(s):  
Breast Cancer ◽  
Colon Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Benzimidazole Derivatives ◽  
Hct 116 ◽  
Mcf 7

Synthesis, Molecular Docking and Biological Evaluation of Novel Flavone Derivatives as Potential Anticancer Agents Targeting Akt

2020 ◽  
Vol 17 (2) ◽  
pp. 158-170 ◽  
Author(s):  
Heba M. Abo-Salem ◽  
Abdullah A Gibriel ◽  
Mohamed E. El Awady ◽  
Adel H. Mandour
Keyword(s):  
Molecular Docking ◽  
Cell Lines ◽  
Anticancer Agents ◽  
Biological Evaluation ◽  
Oxidative Cyclization ◽  
Breast Cancer Cell Lines ◽  
Moderate Activity ◽  
Hct 116 ◽  
Flavone Derivatives ◽  
Mcf 7

Background: Flavonoids are naturally occurring compounds with versatile healthpromoting effects against various diseases. Objective: This aim of this paper is to synthesize and evaluate the biological activity of novel flavone derivatives against cancer. Methods: A new series of 2-hydroxy-α,β-unsaturated ketones 2a-h, was synthesized via the reaction of N-substituted-indole-3-carboxaldehyde 1a-h with 2-hydroxy acetophenone in the presence of piperidine. The oxidative cyclization of 2a-h using hydrogen peroxide/KOH and/or dimethyl sulfoxide/I2 produced the corresponding 2-(N-substituted-1H-indol-3-yl)-3-hydroxy-4H-chromen- 4-ones 3a-h and 2-(N-substituted-1H-indol-3-yl)-4H-chromen-4-ones 4a-h, respectively. Antiproliferative activities for synthesized series were investigated against HCT-116 colon and MCF- 7 breast cancer cell lines. Molecular downstream effects were evaluated using RT-PCR. Moreover, molecular docking was carried out to pinpoint the binding mode of the most active compounds into the active site of Akt enzyme (PDB ID: 3QKK). Results: All compounds exhibited an anti-proliferative activity range of 52-97% and 67.2-99% against HCT-116 and MCF-7, respectively. Compounds 3b, 3h, 3g and 4h had a minimal inhibitory effect on normal BJ1 cells indicating their safety profile. Compounds 3b and 4h, in particular, exhibited the most potent antiproliferative activity against HCT116 and MCF7, meanwhile compounds 3g, 3h and 4g showed potent to moderate activity. Compound 3b had IC50 of 78.3 μM and 53.9 μM against HCT-116 and MCF-7 respectively with comparable IC50 for doxorubicin of 65.1 μM and 45.02 μM. Compound 3b exhibited significant down-regulation for Akt and significant up-regulation of CAS9 and CDKN1genes in all tested cell lines. Conclusion: The synthesized flavone derivatives and particularly compound 3b exhibited promising anticancer activity through Akt inhibition.

scholarly journals PHYTOCHEMICAL COMPOSITION AND ANTICANCER ACTIVITY OF SEAWEEDS ULVA LACTUCA AND EUCHEUMA COTTONII AGAINST BREAST MCF-7 AND COLON HCT-116 CELLS

2016 ◽  
Vol 9 (6) ◽  
pp. 115 ◽  
Author(s):  
Ade Arsianti Arsianti ◽  
Fadilah Fadilah ◽  
Kusmardi Suid ◽  
Fatmawaty Yazid ◽  
Lies Kurniati Wibisono ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Positive Result ◽  
Ethyl Acetate ◽  
Anticancer Activity ◽  
Ulva Lactuca ◽  
Phytochemical Composition ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Eucheuma Cottonii ◽  
Mcf 7

Objective: this study is aimed to develop marine resources which is focused on the determination of  phytochemical composition and exploration of seaweeds Ulva Lactuca and Eucheuma cotonii, as a potential  anti-breast cancer and anti-colorectal cancer agents. Methods: Seaweeds Ulva Lactuca collected from Parangtritis beach, Yogyakarta, Central Java, Indonesia. Whereas Eucheuma cottonii collected from Salemo island, South Sulawesi, Indonesia. Seaweeds U. lactuca and E. cottonii were macerated in organic solvents, n-hexane, chloroform, ethyl acetate and ethanol, respectively. After maceration for three days, the mixture was filtered, the filtrate was concentrated by rotary evaporator. The concentrated extract of n-hexane, ethyl acetate, ethanol and chloroform were then analyzed by thin layer chromatography. Phytochemical test of the concentrated extract were conducted to identify the metabolites containing in the seaweeds. Furthermore, the cytotoxic activity of the n-hexane, ethyl acetate, ethanol and chloroform extract of Ulva Lactuca and Eucheuma cotonii were evaluated as a growth inhibitor of breast MCF-7 and colorectal HCT-116 cancer cells by MTT cell proliferation assay. Results: Phytochemical test  for the  concentrated extracts of Ulva Lactuca showed the positive result for metabolites of  steroids, glycosides, flavonoid,and tannin. While  the concentrated extracts of E. cottonii showed positive result for metabolites of steroids, glycosides, and flavonoid. Both concentrated extracts of Ulva lactuca and Eucheuma cotonii exhibited anticancer activity against breast MCF-7 and colorectal HCT-116 cells with IC50 ranging of  21 µg/mL  to  99 µg/mL . Conclusion: Our results clearly demonstrate seaweeds Ulva Lactuca and Eucheuma cotonii as a promising candidates for the  new anti-breast and anti-colorectal cancer agents. Keywords: Phytochemistry, Ulva Lactuca, Eucheuma cotonii , anticancer, breast MCF-7, colorectal HCT-116

scholarly journals A Radioligand Binding Assay for Antitubulin Activity in Tumor Cells

2005 ◽  
Vol 11 (1) ◽  
pp. 82-89 ◽  
Author(s):  
David H. Young ◽  
Fernando M. Rubio ◽  
Paul O. Danis
Keyword(s):  
Tumor Cells ◽  
Binding Assay ◽  
Radioligand Binding ◽  
Covalent Binding ◽  
Cytotoxic Agents ◽  
Competitive Binding Assay ◽  
A Cell ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Tubulin Mutations

The benzamide RH-5854 is shown to be highly potent toward tumor cells and to arrest nuclear division by a highly specific covalent binding to the β-subunit of tubulin in the colchicine binding region. Binding of 3H-RH-5854 to β-tubulin in HCT-116 colon cancer cells is saturable and has been exploited in the development of a cell-based competitive binding assay, which allows antitubulin effects to be detected inwhole cells. 3H-RH-5854 binding is strongly inhibited by preincubating the cells with compounds that bind to the colchicine site andwith paclitaxel. Binding of 3H-RH-5854 is enhanced by preincubating the cells with vinblastine but not by other agents that bind at or near the vinblastine site (ansamitocin P-3 and phomopsin A). Various cytotoxic agents that do not act on tubulin do not affect binding of 3H-RH-5854 in HCT-116 cells, demonstrating specificity of the assay for detection of antitubulin activity. As an alternative to traditional assays that employ isolated brain tubulin, the 3HRH-5854 binding assay enables screening for antitubulin effects directly in tumor cells, providing an assay that accounts for cell-specific criteria that influence sensitivity such as different tubulin isotypes, tubulin mutations, drug metabolism, and efflux mechanisms.

scholarly journals Anti-Proliferative and Pro-Apoptotic Activities of Hederacolchiside A1 On MCF-7 Cells Via ROS Regulation and JAK2/STAT3 Inactivation

2021 ◽  
Author(s):  
Aijun Chen ◽  
Shushu Zhang ◽  
Dandan Zhang ◽  
Xingjiang Hu ◽  
Nana Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ros Generation ◽  
Caspase 9 ◽  
Apoptotic Pathway ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Induced Apoptosis ◽  
Mcf 7

Abstract Many studies have shown that hederacolchiside A1 (HA1) is an important anticancer saponin, although its mechanism of action and in vivo investigations are still lacking. Our previous results revealed that HA1 may have the potential to treat breast cancer. Therefore, we attempted to verify the potential anti-breast cancer effect of HA1 in vitro and in vivo. MTT, flow cytometry, DCFH-DA fluorescence microscopy, and western blotting were used to evaluate the activities and mechanisms of action of HA1. Athymic nude mice were used to demonstrate the antitumor activity of HA1 in vivo. HA1 exhibited significant cytotoxic effects on HepG2, MCF-7, MDA-MB-231, SKBr-3, HT-29, and HCT-116 cells, especially MCF-7 cells. HA1 blocked the sub-G1 and G0/G1 phases, induced apoptosis, promoted reactive oxygen species (ROS) generation, and decreased the mitochondrial membrane potential of MCF-7 cells. HA1 upregulated Bax and downregulated Bcl-2 levels and activated caspase-9 and caspase-3 in MCF-7 cells Meanwhile, HA1 inhibited the phosphorylation of JAK2/STAT3 in MCF-7 cells. In addition, 50 and 100 mg/kg HA1 significantly inhibited the growth of transplanted tumors with inhibition rates of 46.95 ± 26.72% and 48.45 ± 22.36%, respectively. This preliminary study demonstrated that HA1 could inhibit proliferation and induce the apoptosis of MCF-7 cells via ROS-mediated activation of the mitochondrial apoptotic pathway and JAK2/STAT3 inactivation. HA1 may therefore be developed as a novel agent for breast cancer therapy.

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

2018 ◽  
Vol 15 (7) ◽  
pp. 995-1004
Author(s):  
Santosh R. Deshmukh ◽  
Shankar R. Thopate
Keyword(s):  
Ascorbic Acid ◽  
Cytotoxic Activity ◽  
Chemical Space ◽  
Uv Light ◽  
General Procedure ◽  
Cancer Cell Line ◽  
Cytotoxic Agents ◽  
Reduced Pressure ◽  
In Series ◽  
Mcf 7

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.

scholarly journals Naproxen Based 1,3,4-Oxadiazole Derivatives as EGFR Inhibitors: Design, Synthesis, Anticancer, and Computational Studies

2021 ◽  
Vol 14 (9) ◽  
pp. 870
Author(s):  
Mohammad Mahboob Alam ◽  
Syed Nazreen ◽  
Abdulraheem S. A. Almalki ◽  
Ahmed A. Elhenawy ◽  
Nawaf I. Alsenani ◽  
...  
Keyword(s):  
Docking Studies ◽  
Biological Data ◽  
Egfr Inhibitors ◽  
Design Synthesis ◽  
Standard Drug ◽  
Egfr Inhibition ◽  
Hct 116 ◽  
Oxadiazole Derivatives ◽  
Hct 116 Cells ◽  
Mcf 7

A library of novel naproxen based 1,3,4-oxadiazole derivatives (8–16 and 19–26) has been synthesized and screened for cytotoxicity as EGFR inhibitors. Among the synthesized hybrids, compound2-(4-((5-((S)-1-(2-methoxynaphthalen-6-yl)ethyl)-1,3,4-oxadiazol-2-ylthio)methyl)-1H-1,2,3-triazol-1-yl)phenol(15)was the most potent compound against MCF-7 and HepG2cancer cells with IC50 of 2.13 and 1.63 µg/mL, respectively, and was equipotent to doxorubicin (IC50 1.62 µg/mL) towards HepG2. Furthermore, compound 15 inhibited EGFR kinase with IC50 0.41 μM compared to standard drug Erlotinib (IC50 0.30 μM). The active compound induces a high percentage of necrosis towards MCF-7, HePG2 and HCT 116 cells. The docking studies, DFT and MEP also supported the biological data. These results demonstrated that these synthesized naproxen hybrids have EGFR inhibition effects and can be used as leads for cancer therapy.

scholarly journals Synthesis and Preliminary Anticancer Activity Assessment of N-Glycosides of 2-Amino-1,3,4-thiadiazoles

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7245
Author(s):  
Katarzyna Żurawska ◽  
Marcin Stokowy ◽  
Patryk Kapica ◽  
Monika Olesiejuk ◽  
Agnieszka Kudelko ◽  
...  
Keyword(s):  
Hela Cells ◽  
Biological Response ◽  
Molecular Iodine ◽  
G1 Phase ◽  
Activity Assessment ◽  
Apoptotic Effect ◽  
Hct 116 ◽  
Thiadiazole Derivatives ◽  
Hct 116 Cells ◽  
Mcf 7

The addition of 2-amino-1,3,4-thiadiazole derivatives with parallel iodination of differently protected glycals has been achieved using a double molar excess of molecular iodine under mild conditions. The corresponding thiadiazole derivatives of N-glycosides were obtained in good yields and anomeric selectivity. The usage of iodine as a catalyst makes this method easy, inexpensive, and successfully useable in reactions with sugars. Thiadiazole derivatives were tested in a panel of three tumor cell lines, MCF-7, HCT116, and HeLa. These compounds initiated biological response in investigated tumor models in a different rate. The MCF-7 is resistant to the tested compounds, and the cytometry assay indicated low increase in cell numbers in the sub- G1 phase. The most sensitive are HCT-116 and HeLa cells. The thiadiazole derivatives have a pro-apoptotic effect on HCT-116 cells. In the case of the HeLa cells, an increase in the number of cells in the sub-G1- phase and the induction of apoptosis was observed.

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