Novel synthesis of nicotinamide derivatives of cytotoxic properties

Girgis, Adel S.; Hosni, Hanaa M.; Barsoum, Flora F.

doi:10.1016/j.bmc.2006.02.031

Cited by 51 publications

(31 citation statements)

References 14 publications

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“…Antitumor Activity In-vitro antitumor activity of the tested compounds was screened utilizing Sulfo-Rodamine B (SRB) standard method 15,[29][30][31][32][33][34][35] in the National Cancer Institute, Cairo University, Egypt. All the prepared target compounds (4a-j, 5a-h) were tested for their antitumor properties against HCT116 "colon" and T47D "breast" cancer cell lines.…”

Section: Resultsmentioning

confidence: 99%

“…Compound 4g was the most effective one with IC 50 =0.00586 mM compared with Doxorubicin (IC 50 =0.00686 mM). This derivative was selected by US-NCI for more antitumor activity screening [30][31][32][33][34][35] The observed data expressed as GI 50 (the concentration resulting in a 50% growth inhibition of the tumor compared with the control experiments), TGI (the concentration resulting in a 100% growth inhibition of the tumor compared with the control experiments) and LC 50 were presented in Table 2. It showed promising activity against 38 cell lines especially, HOP-92, NCI-H226 (non-small cell lung cancer), GI 50 =0.000865, 0.00127 mM, respectively, SF-539, SNB-75 (CNS cancer), GI 50 =0.00144, 0.000811 mM, respectively, MALME-3M, SK-MEL-5 (melanoma), GI 50 =0.0016, 0.0015 mM, respectively, OVCAR-4, SK-OV-3 (ovarian cancer), GI 50 =0.00102, 0.00115 mM, respectively, 786-0, A498, RXF 393, UO-31 (renal cancer), GI 50 =0.00112, 0.00111, 0.00118, 0.00148 mM, respectively and MDA-MB-231/ATCC, HS 578T (breast cancer), GI 50 =0.00133, 0.00113 mM, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…The crystallographic data were collected at T=298 K on a Kappa CCD Enraf Nonius FR 590 diffractometer using a graphite monochromator with Mo-Kα radiation (λ= 0.71073 Å). The crystal structures were determined by SIR92 43) and refined by maXus 44) Antitumor Activity The potential cytotoxicity of the tested compounds was evaluated using the method of Skehan et al 15,[29][30][31][32][33][34][35] Cells were plated in 96-multiwell plate (10 4 cells/ well) for 24 h before treatment with the prepared compounds to allow the attachment of cells to the wall of the plate. The tested compounds were dissolved in dimethylsulfoxide (DMSO) and diluted 1000-fold in the assay.…”

Section: )mentioning

confidence: 99%

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Facile Synthesis and Quantitative Structure–Activity Relationship Study of Antitumor Active 2-(4-Oxo-thiazolidin-2-ylidene)-3-oxo-propionitriles

Hanna

George

2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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2-(5-Arylidene-4-oxo-3-phenyl-thiazolidin-2-ylidene)-3-oxo-propionitriles 4a-j were prepared via condensation of aromatic aldehydes with 4-thiazolidinones 3a, b. The latter was obtained via electrophilic attack of phenylisothiocyanate on 3-oxo-propionitriles 1a, b followed by reaction with chloroacetyl chloride under basic condition. Additionally, 2-(5-heteroalicyclic methylene) analogues 5a-h were prepared via Mannich reaction of the appropriate secondary amines and formaldehyde with 4-thiazolidinones 3a, b. Many of the synthesized compounds exhibited promising antitumor properties against colon HCT116 and breast T47D cell lines. 3D-Pharmacophore modeling and quantitative structure-activity relationship (QSAR) analysis were combined to explain the observed antitumor properties.Key words thiazolidinone; quantitative structure-activity relationship; antitumor activity; 3-oxo-propionitrile; HCT116; T47D Cancer ranks second in diseases leading to mortality, following only cardiovascular diseases. One-quarter of all deaths in the United States are caused by cancer.1) Out of the many cancer diseases, breast cancer is the most prevalent cancer in women and represents the second highest leading cause of cancer death in this population after lung cancer.2) Colorectal cancer is the third most common cancer in both men and women, 91% of cases are diagnosed in individuals 50 years of age and older. 1) Chemotherapy is widely used to treat and control cell growth and limit the spread of cancer cells to other sites. Although, there is a success with certain forms of cancer, drug therapy has only limited impact against the three major killers: carcinoma of lung, breast and colorectal system. Therefore, there is a need to develop novel antitumor agents to treat and combat this disease.Several promising antitumor agents containing thiazolidine and thiazolidinone scaffolds have been identified to have a broad range of anticancer activities.3-14) Previously, we reported promising antitumor properties of a variety of 5-arylidene thiazolidinone derivatives Ia-c (Fig. 1) exhibiting considerable cytotoxic activity against colon HCT116 cancer cell lines compared with Doxorubicin (reference standard, IC 50 =0.00686 mM).15) In continuation of these previous findings and in order to optimize novel antitumor active agents possessing the same thiazolidinone core, it is intended in the present work to perform some modifications in the adopted structures via inserting heteroalicyclic amines (morpholinyl or piperidinyl functions, 4a-j) instead of the aromatic amines Ia-c due to their hydrophilic properties. Moreover, a series of heteroalicyclic methylene containing compounds 5a-h will be also prepared replacing the arylidene moiety of Ia-c (Fig. 1). Additionally, many morpholine and piperidine containing compounds were known as anticancer active agents that exerted their actions via inhibition of different targets such as phosphatidylinositol 3-kinases (PI3Ks) and histone deacetylase (HDAC). [16][17][18][19][20] Moreover, the piperidine deriva...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: )mentioning

confidence: 99%

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Facile Synthesis and Quantitative Structure–Activity Relationship Study of Antitumor Active 2-(4-Oxo-thiazolidin-2-ylidene)-3-oxo-propionitriles

Hanna

George

2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…Pyridine derivatives have been shown to exhibit anticancer (Girgis et al 2006) and antiviral (Hamdouchi et al, 1999) activities. As part of our studies in this area we synthesized the title compound and report herein on its synthesis and crystal structure.…”

Section: Structure Descriptionmentioning

confidence: 99%

2-Amino-3-methylpyridinium 4-methoxybenzoate

et al. 2016

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In the title molecular salt, C 6 H 9 N 2 + ÁC 8 H 7 O 3 À , the cation is protonated at its pyridine N atom and is inclined by 3.39 (9) to the benzene ring of the anion, which is deprotonated at the carboxyl group. The methoxy group is twisted with respect to the benzene ring to which it is attached, the methyl C atom deviating from the ring plane by 0.023 (2) Å . In the crystal, the anions and cations are linked by two N-HÁ Á ÁO hydrogen bonds, forming an R 2 2 (8) ring motif. They are also linked by a weak offset -interaction [centroid-to-centroid distance = 3.890 (1) Å ]. The anions and cations are further connected through N-HÁ Á ÁO and C-HÁ Á ÁO hydrogen bonds, forming slabs parallel to (001). Structure descriptionPyridine derivatives have been shown to exhibit anticancer (Girgis et al. 2006) and antiviral (Hamdouchi et al., 1999) activities. As part of our studies in this area we synthesized the title compound and report herein on its synthesis and crystal structure.The geometric parameters of the title compound, Fig. 1, are comparable with those reported for similar structures (Babu et al., 2014;Sivakumar et al., 2016). The asymmetric unit contains a 2-amino-3-methylpyridinium cation, which is protonated at the pyridine N atom and a 4-methoxybenzoate anion which is deprotonated at the carboxyl group. They are linked by two N-HÁ Á ÁO hydrogen bonds, forming R 2 2 (8) ring-motifs (Table 1 and Fig. 2). They are also linked by a weak offset -interaction [Cg1Á Á ÁCg2 = 3.890 (1) Å , interplanar distance = 3.487 (1) Å , slippage = 1.896 Å , Cg1 and Cg2 are the centroids of rings C1-C6 and N1/C9-C13, respectively]. The benzene ring (C1-C6) makes a dihedral angle of 3.39 (9) with the pyridine ring (N1/C9-C13). The methoxy group is twisted with respect to the benzene ring, the methyl atom C17 deviating from the ring plane by 0.023 (2) Å . The mean plane of the methoxy group (C1/O1/C7) is twisted at an angle of 3.49 (17) with respect to the attached benzene ring.

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“…Erlotinib specifically targets of the EGFR tyrosine kinase, which is highly expressed and occasionally mutated in various forms of cancer. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor 62 . For the signal to be transmitted, two members of the EGFR family need to come together to form a homo-dimer.…”

Section: Molecular Modelling Study Of Egfr Inhibitor and Binding Confmentioning

confidence: 99%

Molecular modeling study bioactive natural product of khellin analogues as a novel potential pharmacophore of EGFR inhibitors

Elgazwy

Edrees

Ismail

2012

Journal of Enzyme Inhibition and Medicinal Chemistry

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Novel synthesis of nicotinamide derivatives of cytotoxic properties

Cited by 51 publications

References 14 publications

Facile Synthesis and Quantitative Structure–Activity Relationship Study of Antitumor Active 2-(4-Oxo-thiazolidin-2-ylidene)-3-oxo-propionitriles

Facile Synthesis and Quantitative Structure–Activity Relationship Study of Antitumor Active 2-(4-Oxo-thiazolidin-2-ylidene)-3-oxo-propionitriles

2-Amino-3-methylpyridinium 4-methoxybenzoate

Molecular modeling study bioactive natural product of khellin analogues as a novel potential pharmacophore of EGFR inhibitors

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