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ABSTRACT: The present work reports the synthesis of 20 novel fluorine-containing quinoline and pyrimido[4,5-b]quinoline derivatives bearing a sulfonamide moiety. The new synthesized compounds were designed in compliance with the general
pharmacophoric requirements for carbonic anhydrase (CA) inhibiting anticancer drugs, as this may play a role in their anticancer
activity. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer
cell line (MCF7). Compounds 11 and 12 exhibited better activities than the reference drug doxorubicin (IC50=71.8μM) with IC50 values of 52.6μM and 67.3μM, respectively. On the other hand, compounds 6, 10, and 13 showed IC50 values (71.8μM, 69.8μM, and 70.8μM, respectively) comparable to that of the reference drug doxorubicin. In addition, docking
of the synthesized compounds into human carbonic anhydrase isozyme II (hCA II) active site was performed in order to predict
the affinity and the orientation of these compounds at the isozyme active site. Also, the most active compounds, 11 and 12, were selected and evaluated for their ability to enhance the cell killing effect of γ-radiation.
KeywordsQuinoline–Fluorine–Sulfonamide–Carbonic anhydrase II–Anticancer–γ-Radiation
Medicinal Chemistry Research 04/2012; 20(3):388-400. · 1.27 Impact Factor
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ABSTRACT: The present work reports the synthesis of some new Schiff bases, 5-(substituted benzylideneamino)-6-cyano-7H-7-(4-methoxyphenyl)-2-(4-sulphamoylphenylamino) pyrano[2,3-d]thiazole (5-15). The design of the structures of these compounds complies with the general pharmacophoric requirements for CA inhibiting anticancer drugs. The newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Most of the screened compounds showed interesting cytotoxic activities compared to doxorubicin as a reference drug. Compounds 4, 6-8 and 11 (IC(50): 27.51, 10.25, 9.55, 9.39 and 9.70 μM, respectively) exhibited higher cytotoxic activities than the reference drug doxorubicin (IC(50): 32.00 μM). Additionally, the previously mentioned compounds were evaluated again for their ability to enhance the cell killing effect of γ-radiation.
European journal of medicinal chemistry 04/2012; 53:403-7. · 3.27 Impact Factor
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ABSTRACT: A series of novel 4-(4-substituted-thiazol-2-ylamino)-N-(pyridin-2-yl) benzene-sulfonamides were synthesized and screened for their cytotoxic activity against human breast cancer cell line (MCF-7). Compounds 6, 7, 9, 10, 11, and 14 displayed significant activity against MCF-7 when compared to doxorubicin, which was used as a reference drug. The synergistic effect of Gamma radiation for the most active derivatives 7, 9, and 11 was also studied and their IC(50) values markedly decreased to 11.9 μM, 11.7 μM, and 11.6 μM, respectively.
Archives of Pharmacal Research 01/2012; 35(1):59-68. · 1.59 Impact Factor
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ABSTRACT: Sulfonamides and quinoxaline derivatives possess many types of biological activities and have been recently reported to show substantial antitumor activity. This paper reports the synthesis of novel thioureido sulfaquinoxaline derivatives. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against a human liver cell line (HEPG2) and showed higher activity than the reference drug doxorubicin. 4-(3-(4-Ethylbenzoate) thioureido)-N-(quinoxalin-2-yl)benzenesulfonamide (9) (IC₅₀ = 15.6 μmol L⁻¹), N-(pyridin-2-yl)-4-(3-(4-(N-quinoxalin-2-yl-sulfamoyl)phenyl)thioureido)benzenesulfonamide (10) (IC₅₀ = 26.8 μmol L⁻¹) and N-(quinoxalin-2-yl)-4-(3-(4-(N-thiazol-2-ylsulfamoyl)phenyl)thioureido)benzenesulfonamide (11) (IC₅₀ = 24.4 μmol L⁻¹) were the most potent compared to doxorubicin (IC₅₀ = 71.8 μmol L⁻¹). The most potent compounds 9, 10 and 11 were evaluated as radiosensitizing agents by subjecting the compounds to γ-irradiation (8 kGy).
Acta Pharmaceutica 12/2011; 61(4):415-25. · 0.91 Impact Factor
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ABSTRACT: Recently, it has been reported that compounds bearing a sulfonamide moiety posses many types of biological activities, including anticancer activity. There are a variety of mechanisms for their anticancer activity, and the most prominent mechanism is the inhibition of carbonic anhydrase (CA) isozymes. The present work reports the synthesis of some new thiazolo[4,5-b]pyrane, thiazolo[4,5-b]pyrano[2,3-d]pyrimidine derivatives bearing a sulfonamide moiety. The design of the structures of these compounds complies with the general pharmacophoric requirements for CA inhibiting anticancer drugs. The newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Most of the screened compounds showed interesting cytotoxic activities compared to doxorubicin as a reference drug. Compounds 5, 6, 10 and 12 (IC(50) values 39.4 μM, 41.6 μM, 35.72 μM and 34.64 μM, respectively) exhibited higher cytotoxic activities than the reference drug doxorubicin (IC(50) = 71.8 μM). Additionally, the previously mentioned compounds were evaluated again for their ability to enhance the cell killing effect of γ-radiation.
European journal of medicinal chemistry 08/2011; 46(10):5120-6. · 3.27 Impact Factor
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ABSTRACT: Pyrroles and pyrrolo[2,3-d]pyrimidines were reported to act as potent anticancer agents, in this work, a series of novel 2-substituted-3-cyano-4-phenyl-pyrrole 5, 6, 11-18, and 5-phenyl-pyrrolo[2,3-d]pyrimidine derivatives 7-10, 19-24 bearing either sulfathiazole or sulfapyridine were synthesized. The structures of these compounds were confirmed by elemental analysis, IR, (1)H NMR and mass spectral data. All the newly synthesized compounds were evaluated for their in vitro cytotoxicity against liver and breast cancer cell line (HEPG2 and MCF7). Most of the screened compounds showed interesting cytotoxic activities compared with the used reference drug (doxorubicin). The radiosensitizing ability of some of the synthesized compounds was studied and the results showed an increase in the cell killing effect of γ-radiation after combination with the tested compounds.
Bioorganic & medicinal chemistry letters 11/2010; 20(21):6316-20. · 2.65 Impact Factor
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ABSTRACT: Sulfonamide bearing compounds possess many types of biological activities and have recently been reported to show substantial antitumor activity in vitro and/or in vivo. There are a variety of mechanisms for the anticancer activity, and the most prominent mechanism is the inhibition of carbonic anhydrase (CA) isozymes. The present work reports the synthesis of twenty novel quinoline and pyrimido[4,5-b]quinoline derivatives bearing a sulfonamide moiety. The new synthesized compounds were designed in compliance with the general pharmacophoric requirements for CA inhibiting anticancer drugs, as this may play a role in their anticancer activity. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Compounds 6, 9 and 18 showed IC(50) values (72.9 microM, 72.1 microM and 71.9 microM, respectively) comparable to that of the reference drug doxorubicin (IC(50) = 71.8 microM). On the other hand, compound 8 exhibited better activity than doxorubicin with an IC(50) value of 64.5 microM. Additionally, the most potent compounds 8 and 18 were evaluated for their ability to enhance the cell killing effect of gamma-radiation.
European journal of medicinal chemistry 09/2010; 45(9):3677-84. · 3.27 Impact Factor
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ABSTRACT: New derivatives of thiophenes 2, 12, iminoaminothieno[2,3-d]pyrimidines 3, 5, and 6, triazolothieno[2,3-d]pyrimidines 8-11, pyrazolo- and triazinothieno[2,3-d]pyrimidines 4, 7, respectively, have been prepared by different synthetic procedures. Structure elucidation of the newly synthesized compounds was carried out via elemental analyses and spectral data. The antitumor activity of compounds 2, 3, and 9-12 was evaluated against in-vitro cell lines (HEPG-2 and MCF-7). Compounds 2, 3, 10, 11, and 12 showed significant in-vitro cytotoxic activity against hepatocellular carcinoma (HEPG-2) compared to the reference drug Doxorubicin. Compound 2 showed significant in-vitro cytotoxic activity against breast cancer (MCF-7) cells compared to the reference drug Doxorubicin. The augmenting effect of gamma-radiation was assessed; here, compounds 2, 3, 10, and 11 showed the most potent in-vitro anticancer activity.
Archiv der Pharmazie 04/2010; 343(7):404-10. · 1.71 Impact Factor
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ABSTRACT: Several novel pyrazole (11-18) and pyrimidine (19-23) derivatives were synthesized starting from different sulfonamides and different active methylenes. The synthesized compounds were characterized by elemental analysis, IR, 1H-NMR and mass spectral data. The obtained compounds were screened as antitumor agents against human tumor cell line. Some of the tested compounds were equipotent while the others were more potent than doxorubicin (CAS 25316-40-9). The synergistic effect with gamma-radiation was also studied.
Arzneimittel-Forschung 01/2010; 60(1):48-55. · 0.72 Impact Factor
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ABSTRACT: Various isomeric structural purine analogues possessing the pyrazolo[3,4-d]pyrimidine nucleus bearing amino acid moieties have been synthesized. The structures of the synthesized compounds were elucidated by spectral data. Preliminary testing for in vitro anticancer activity of the synthesized compounds against Ehrlich ascites carcinoma cells was carried out. 2-(1-Phenyl-1H-pyrazolo [3,4-d]pyrimidin-4-ylamino)-propanoic acid (3 d), 4-methyl-2-(1-phenyl-1H-pyrazolo [3,4-d] pyrimidin-4-ylamino)-pentanoic acid (3 d), 4-methylthlo-2-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)-butanoic acid (3e) and phenyl-2-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)propanoic acid (3f) were the most active compounds. Moreover, compounds 3e and 1-(1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-pyrrolidine-2-carboxylic acid (4) exhibited significant in vivo radioprotective activity.
Arzneimittel-Forschung 02/2009; 59(2):96-103. · 0.72 Impact Factor
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ABSTRACT: Novel pyrrolo[2,3-d]pyrimidine derivatives 4a-e, 10, 14, 15, pyrazolopyrrolopyrimidine 13, pyrrolotriazolopyrimidine 5-9, 17 and pyrrolopyrimidotriazine 18 are reported herein. The design of these compounds was based upon the molecular modeling simulation of the fitting values and conformational energy values of the best-fitted conformers to VEGFRTK inhibitor hypothesis. This hypothesis was generated from its corresponding lead compounds using CATALYST software. The structures of these compounds were confirmed by microanalyses, IR, (1)H NMR, and mass spectral data. Compounds 6 and 15 showed interesting in vitro antitumor activity compared to doxorubicin as positive control. These results are nearly consistent with the molecular modeling studies. Docking studies were made on compound 15 to predict its binding mode. Moreover, compound 10 exhibited a significant radioprotective activity.
Bioorganic & medicinal chemistry 04/2008; 16(5):2391-402. · 2.82 Impact Factor
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ABSTRACT: The present work reports the possible utility of 4-(5,5-dimethyl-3-oxo-cyclohex-1-enylamino)benzenesulfonamide in the synthesis of some novel 4-(quinolin-1-yl) benzenesulfonamide derivatives (6a-o). Structures of the newly synthesized compounds were confirmed by elemental analyses and spectral data. All the newly synthesized compounds were evaluated for their in vitro anticancer activity. Compounds 6k, 6j and 6m showed interesting cytotoxic activity compared with doxorubicin (CAS 23214-922-8) as a reference drug. Additionally, compound 6c exhibited in vivo radioprotective activity, against gamma-irradiation, in mice.
Arzneimittel-Forschung 02/2008; 58(1):35-41. · 0.72 Impact Factor
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ABSTRACT: Some novel 4-(quinolin-1-yl)-benzenesulfonamide and 4-(pyrimido[4,5-b]quinolin-10-yl)-benzenesulfonamide derivatives have been synthesized. All the newly synthesized target compounds were subjected to in vitro cytotoxic screening to be evaluated for their anticancer activity against Ehrlich ascites carcinoma cells. Among these new compounds, compounds 9a, 11, 12b, 18 and, in particular, 19 showed promising in vitro cytotoxic activity compared with doxorubicin (CAS 23214-92-8) as a reference drug. Moreover, compound 8 exhibited in vivo radioprotective activity against gamma-irradiation in mice.
Arzneimittel-Forschung 02/2007; 57(12):795-803. · 0.72 Impact Factor
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ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
ChemInform 10/2006; 37(43).
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ABSTRACT: A novel series of pyrrolo[2,3-d] pyrimidines bearing sulfonamide moieties have been synthesized and tested for their antitumor activity. Among them, compounds 4, 8b, Bd, 8g and 14 showed promising antitumor activity. Moreover, compound 8d exhibited radioprotective activity. The structures of the newly synthesized compounds were established by their elemental analyses and spectral data.
Arzneimittel-Forschung 02/2006; 56(4):301-8. · 0.72 Impact Factor
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ABSTRACT: Several sulfonamides having pyrrole (5a-c, 8, 11b-19, 23, 24), pyrrolo[2,3-d] pyrimidine (6, 7, 10, 20, 21, 25) and pyrrolo[2,3-b]pyridine (22) were synthesized and evaluated for their antitumor and radioprotective activities. The structure of the synthesized compounds was elucidated by elemental analyses and spectral data. Compounds 5a, 16, 17, 19, and 23 displayed more potent antitumor activities than the reference drug, doxorubicin. On the other hand compounds 19, 23 and 25 exhibited radioprotective activities.
Arzneimittel-Forschung 02/2006; 56(6):405-13. · 0.72 Impact Factor
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ABSTRACT: During research on anticancer and radioprotective heterocyclic compounds containing thiophene ring 5-10, 15, 19, thieno[2,3-d]pyrimidines 11-14 and biscompound having thieno[2,3-d]pyrimidine 18 were synthesized. The synthesized compounds were characterized by elemental ananlysis, IR, 1H-NMR and mass spectral data. Some of the obtained compounds showed interesting antitumor and radioprotective activities.
Arzneimittel-Forschung 02/2006; 56(7):553-60. · 0.72 Impact Factor
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ABSTRACT: The syntheses of novel 1,2,4-triazolothienopyrimidine derivatives (4a,b), thiourea derivatives (5-8) and biscompounds having a thieno[2,3-d]pyrimidine nucleus (13-16) utilizing the 2-isothiocyanato derivatives 2a,b are reported. The structures of these compounds were confirmed by microanalysis, IR, 1H-NMR and mass spectrometry. Preliminary biological studies of some synthesized compounds showed promising antitumor and radioprotective activities.
Arzneimittel-Forschung 02/2006; 56(8):593-9. · 0.72 Impact Factor
