Design and Synthesis of Tetrahydroisoquinoline Derivatives as AntiAngiogenesis and Anti-Cancer Agents

Aim: : The aim of our research work is the synthesis of tetrahydroisoquinoline derivatives as anti-Angiogenesis and anti-cancer agents. Background: : Cancer is the second leading cause of deaths in United States. The current recovery rate from the advanced treatment for the cancer is unacceptably low. Therefore, identification of novel, potent and less toxic anticancer agents remains a top priority. Objective: To 1) evaluate anti-angiogenesis, anticancer activities of THIQs on different colorectal cancer cell lines (CRC) viz., Colo320, DLD-1, HCT116, SNU-C1, SW480 and GSK3b in pre-treated viability HCT116. 2) Undertake molecular docking studies of THIQs. Methods: Twenty synthesized THIQs were screened in the Eli Lilly’s Open Innovation Drug Discovery Program and selected twelve compounds for in vitro primary screening in the KRas (Kirsten rat sarcoma)-Wnt SL (Synthetic Lethal) in the basal viability of different colon cancer cell lines. Docking studies of the active THIQs were also performed in our laboratory, targeting the active sites of KRas and VEGF receptors. Results: Compound GM-3-18 was found to possess significant activities for KRas inhibition, with IC50 values in the rage of 0.9 µM to 10.7 µM, for all colon cancer cell lines. Compound GM-3-121 showed potent anti-angiogenesis activity with IC50 = 1.72 µM. Molecular docking studies showed that the carbonyl oxygen atoms of GM-3-18 and GM-3-121 showed hydrogen bonding interactions with the hydrogen of - OH groups of THR 74 (A). Conclusion: The results indicated that all the compounds showed moderate to high activity for KRas inhibition. The THIQs bearing the chloro group at the 4-postiton of the phenyl ring (GM-3-18) exhibited significant KRas inhibition against all colon cancer cell lines.

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Synthesis of 3-Trifluoromethyl-5,6-dihydro-[1,2,4]triazolo Pyrazine Derivatives and Their Anti-Cancer Studies

Molbank ◽

10.3390/m1173 ◽

2020 ◽

Vol 2020 (4) ◽

pp. M1173

Author(s):

Rajaiah Raveesha ◽

Malavalli Guruswamy Dileep Kumar ◽

Salekoppal Boregowda Benaka Prasad

Keyword(s):

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Apoptotic Pathway ◽

Mitochondrial Apoptotic Pathway ◽

Colon Cancer Cell Lines ◽

Anti Cancer ◽

Ht 29

The synthesis of a wide variety of 3-trifluoromethyl-5,6-dihydro-[1,2,4]triazolo pyrazine derivatives, by the treatment of 3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-α]pyrazine hydrochloride with an array of isocyanates in the presence of triethylamine, is reported. All the target compounds were synthesized in excellent yields under mild reaction conditions. The target molecules were effectively screened for their anti-cancer properties and the results are promising. The resultant compounds were assessed for their antiproliferative action against two human colon cancer cell lines (HCT-116 and HT-29 colon cancer cell lines). The IC50 range was estimated at 6.587 to 11.10 µM showing that compound RB7 had remarkable anticancer movement on HT-29. Additionally, it was discovered that RB7 incited the mitochondrial apoptotic pathway by up-regulating Bax and down-regulating Bcl2, eventually leading to the activation of Caspase 3 in HT-29 cells and initiation of cell death via the mitochondrial apoptotic pathway.

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Anti-cancer effects of 2-oxoquinoline derivatives on the HCT116 and LoVo human colon cancer cell lines

Molecular Medicine Reports ◽

10.3892/mmr.2015.4451 ◽

2012 ◽

Vol 12 (6) ◽

pp. 8062-8070 ◽

Cited By ~ 5

Author(s):

FENG-QI FANG ◽

HUI-SHU GUO ◽

JIE ZHANG ◽

LI-YING BAN ◽

JI-WEI LIU ◽

...

Keyword(s):

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Human Colon ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Human Colon Cancer Cell ◽

Human Colon Cancer ◽

Colon Cancer Cell Lines ◽

Anti Cancer

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Anti-cancer effect of Indanone-based thiazolyl hydrazone derivative on colon cancer cell lines

The International Journal of Biochemistry & Cell Biology ◽

10.1016/j.biocel.2019.02.004 ◽

2019 ◽

Vol 110 ◽

pp. 21-28 ◽

Cited By ~ 5

Author(s):

Silpa Narayanan ◽

Pranav Gupta ◽

Urooj Nazim ◽

Mohsin Ali ◽

Nishant Karadkhelkar ◽

...

Keyword(s):

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Colon Cancer Cell Lines ◽

Anti Cancer ◽

Hydrazone Derivative

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INVITRO EVALUATION OF ANTI-CANCER ACTIVITY OF 5-FLOUROURACIL AND CURCUMIN IN SINGLE AND COMBINED FORMS AGAINST BREAST AND COLON CANCER CELL LINES.

International Journal of Advanced Research ◽

10.21474/ijar01/606 ◽

2016 ◽

Vol 4 (6) ◽

pp. 1649-1657 ◽

Cited By ~ 1

Author(s):

Said abdeldayem. ◽

Keyword(s):

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Colon Cancer Cell Lines ◽

Anti Cancer ◽

Cancer Activity

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Synthesis of Piperidine Conjugated Dihydroquinazolin-4(1H)-ones and their Antiproliferative Activity, Molecular Docking Studies and DFT Calculations

Letters in Drug Design & Discovery ◽

10.2174/1570180816666190613120349 ◽

2019 ◽

Vol 17 (1) ◽

pp. 85-93 ◽

Cited By ~ 1

Author(s):

Kereyagalahally Honneshappa Narasimhamurthy ◽

Chandra ◽

Toreshettahally Ramesh Swaroop ◽

Swamy Jagadish ◽

Kanchugarakoppal Subbegowda Rangappa

Keyword(s):

Colon Cancer ◽

Molecular Docking ◽

Amino Acid ◽

Dft Calculations ◽

Cell Lines ◽

Active Sites ◽

Docking Studies ◽

Colon Cancer Cell ◽

Molecular Docking Studies ◽

Colon Cancer Cell Lines

Background: Xanthatin, fluoropyrimidine and thienopyrimidine, pyrazolopyrimidine, pyrimidine carboxamides, and SKLB1002 are reported as VEGFR2 tyrosine kinase inhibitors. Recently, many studies related to different heterocycles conjugated with dihydroquinazolinones are known to have very good biological activities. In this study, we are intended to explore the cytotoxic studies of piperidine conjugated dihydroquinazolinones against colorectal/colon cancer cell lines and along with molecular docking studies and DFT calculations. Methods: The colorectal/colon cell lines HCT116 and A549 cell lines were treated with these compounds and cytotoxic activities were evaluated by MTT dye uptake method. We performed molecular modelling for compound 3d using the Auto Dock software. The binding of compound 3d with target proteins was studied with the collection of experimentally determined PDB database. Optimized geometry by DFT calculations was performed with B3LYP/6-31G (d) basis set. Results: Piperidine-conjugated dihydroquinazolinone analogues displayed anticancer activity. Particularly, the compound 3d with electron-withdrawing substituents on a phenyl ring showed significant cytotoxicity against HCT116 and A549 cell lines. Molecular docking studies proved that the compound 3d has good fitting by forming hydrogen bonds with amino acid residues at the active sites of VEGFR2. The HOMO, LUMO, their energies and UV visible spectrum were predicted using DFT calculations. Conclusion: Four piperidine-conjugated dihydroquinazolinones were synthesized and evaluated against colorectal and colon cancer cell lines. Compound 3d significantly inhibited the growth of HCT116 and A549. Molecular docking studies displayed good fitting of compound 3d by forming different H-bonds with the amino acid at the active sites of the VEGFR2 target. Using a theoretical approach, we optimized HOMO and LUMO plots for the compound 3d.

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Isolation of Cardamonin and Pinostrobin Chalcone from the Rhizomes of Boesenbergia rotunda (L.) Mansf. and their Cytotoxic Effects on H-29 and MDA-MB-231 Cancer Cell Lines

The Natural Products Journal ◽

10.2174/2210315509666190117151542 ◽

2019 ◽

Vol 9 (4) ◽

pp. 341-348 ◽

Cited By ~ 4

Author(s):

Ibrahim Awad Mohammed ◽

Muhammad Nadeem Akhtar ◽

Foo Jhi Biau ◽

Yin Sim Tor ◽

Seema Zareen ◽

...

Keyword(s):

Breast Cancer ◽

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Chemical Constituents ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Colon Cancer Cell Lines ◽

Ht 29

Background: Breast cancer and human colon cancer are the most common types of cancer in females and males, respectively. Breast cancer is the most common type of cancer after lung and colon cancers. Natural products are an important source for drug discovery. Boesenbergia rotunda (L.) Mansf. is commonly known as finger root, belonging to the Zingiberaceae family. Objective: The aim of this study to isolate some natural compounds from the rhizomes of B. rotunda (L.) Mansf., and to investigate their cytotoxicity against the human triple-negative breast cancer cell (MDA-MB-231) and HT-29 colon cancer cell lines. Methods: The dried rhizomes of B. rotunda were extracted with methanol. The methanolic extract was further used for solvent-solvent extraction. Bioassay-guided extraction and isolation of the rhizomes of the B. rotunda exhibited cytotoxic properties of hexane and dichloromethane fractions. Results: Six major chemical constituents, pinostrobin (1), pinostrobin chalcone (2), cardamonin (3), 4,5-dihydrokawain (4), pinocembrin (5), and alpinetin (6) were isolated from the rhizomes of the B. rotunda. All the chemical constituents were screened against the human triple-negative breast cancer cell (MDA-MB-231) and HT-29 colon cancer cell lines. The compound cardamonin (3) (IC50 = 5.62±0.61 and 4.44±0.66 µg/mL) and pinostrobin chalcone (2), (IC50 = 20.42±2.23 and 22.51±0.42 μg/mL) were found to be potent natural cytotoxic compounds against MDA-MB-231 and HT-29 colon cancer cell lines, respectively. Conclusion: Cardamonin (3) and pinostrobin chalcone (2) were found to be the most potential natural compounds against breast cancer cell line MDA-MB-231 and colon cancer HT-29 cell line.

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Reactivity of Monoclonal Antibodies Directed against Lung Cancer Antigens with Human Lung, Breast and Colon Cancer Cell Lines

Disease Markers ◽

10.1155/1993/619781 ◽

1993 ◽

Vol 11 (5-6) ◽

pp. 225-237

Author(s):

Udo Schumacher ◽

Dhia Mukthar ◽

Thomas Schenker

Keyword(s):

Breast Cancer ◽

Lung Cancer ◽

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Breast Cancer Cell Lines ◽

Cancer Antigens ◽

Colon Cancer Cell Lines

A panel of monoclonal antibodies (n=72 including controls) directed against lung cancer antigens was screened immunohistochemically against a panel of seven human lung cancer cell lines (including small cell carcinoma, squamous cell carcinoma, adenocarcinoma and mesothelioma), six human breast cancer cell lines and one human colon cancer cell line, The majority of the antibodies (n=42) reacted also with antigens present on breast and colon cancer cell lines, This cross reactivity especially between lung and breast cancer cell lines is not altogether unexpected since antigens common to breast and lung tissue including their neoplasms such as MUC1 antigen have been described, Our results indicate that epitopes shared by lung and breast cancers are probably more common than previously thought. The relevance for prognosis and therapy of these shared antigens, especially as disease markers in breast cancer, has to be investigated.

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