Fatma A. Ragab

Synthesis of some new pyrazolo[3,4-d]pyrimidine derivatives of expected anticancer and radioprotective activity

On the account of the reported anticancer activity of pyrazolo[3,4-d]pyrimidines, a new series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized and tested for in-vitro anticancer activity against Ehrlich Ascites Carcinoma (EAC) cell line. Moreover, one of the target products was evaluated for in-vivo radioprotective activity. The reaction of o-aminoester 1 with benzylamine in presence of triethylorthoformate yielded the corresponding 5-benzylpyrazolopyrimidine derivative 2. The N-amino derivative 3 was used to synthesize new derivatives of pyrazolopyrimidines 4-7. The corresponding 1,3,4-oxadiazolopyrazolopyrimidine derivatives 12 and 14 were obtained via reaction of compound 9 with reagent 10 and/or triethylorthoformate. Thiophosgenation of compound 1 furnished the corresponding 5-isothiocyanate derivative 15, which was reacted with o-phenylenediamine, thiosemicarbazide and anthranilic acid to give benzimidazolopyrazolopyrimidine, 17, pyrazolotriazolopyrimidine, 19 and pyrazolopyrimidobenzoxazine, 20 respectively. The structures of the synthesized compounds were confirmed by microanalyses, IR, NMR, and mass spectral data. Compounds 2 and 9 showed intermediate anticancer activity compared to doxorubicin as positive control with IC50 values of 90 and 100 microg/ml, respectively. On the other hand, compound 5 showed significant radioprotective effect.

Design, synthesis and anticancer evaluation of novel tetrahydroquinoline derivatives containing sulfonamide moiety

Sulfonamides poses 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 of these is through the inhibition of carbonic anhydrase isozymes. The present work reports the synthesis of some novel quinoline and pyrimido[4,5-b]quinoline derivatives bearing a substituted or unsubstituted sulfonamide moiety. The design of the structures of these compounds complies with the general pharmacophore of the sulfonamide compounds that act as carbonic anhydrase (CA) inhibitors as this may play a role in their anticancer activity. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against breast cancer cell line (MCF7). Most of the screened compounds showed interesting cytotoxic activities compared to a reference drug.

In vitro anticancer screening and radiosensitizing evaluation of some new quinolines and pyrimido[4,5-b]quinolines bearing a sulfonamide moiety

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.

Synthesis of novel pyrrole and pyrrolo[2,3-d]pyrimidine derivatives bearing sulfonamide moiety for evaluation as anticancer and radiosensitizing agents

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.

Synthesis of novel 1,3,4-trisubstituted pyrazoles as anti-inflammatory and analgesic agents.

Some novel 1,3,4-trisubstituted pyrazoles were synthesized and screened for their anti-inflammatory and analgesic activities as well as their ulcerogenic liability. They showed anti-inflammatory and analgesic activities with better GIT tolerance than the standard drug phenylbutazone. In addition, IC50 values for 5e and 8e were recorded. Compound 5e was found to be the most active one as anti-inflammatory and analgesic agent. On the other hand, COX-1/COX-2 isozyme selectivity was also done which showed equal inhibition to both isoforms.

Anticancer and radio-sensitizing evaluation of some new thiazolopyrane and thiazolopyranopyrimidine derivatives bearing a sulfonamide moiety.

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.

Synthesis, in vitro anticancer screening and radiosensitizing evaluation of some new 4-[3-(substituted)thioureido]-N-(quinoxalin-2-yl)-benzenesulfonamide derivatives

Synthesis, in vitro anticancer screening and radiosensitizing evaluation of some new 4-[3-(substituted)thioureido]-N-(quinoxalin-2-yl)-benzenesulfonamide derivatives 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). Sinteza, in vitro antitumorsko ispitivanje i radiosenzitirajuće vrednovanje novih derivata 4-[3-(supstituiranih)tioureido]-N-(kinoksalin-2-il)benzensulfonamida Derivati sulfonamida i kinoksalina imaju raznoliko biološko djelovanje, između ostalog i antitumorsko djelovanje. U radu je opisana sinteza novih derivata tioureido sulfakinoksalina. Svim novim spojevima ispitano je antitumorsko djelovanje in vitro na humanoj staničnoj liniji jetre (HEPG 2). Svi ispitani spojevi pokazuju jači učinak nego referentni lijek doksorubicin. Najjači učinak imali su 4-(3-(4-etilbenzoat)tioureido)-N-(kinoksalin-2-il)benzensulfonamid (9) (IC50 = 15,6 μmol L-1), N-(piridin-2-il)-4-(3-(4-(N-kinoksalin-2-il-sulfamoil)fenil)tioureido)-benzensulfonamid (10) (IC50 = 26,8 μmol L-1) i N-(kinoksalin-2-il)-4-(3-(4-(N-tiazol-2-ilsulfamoil)fenil)tioureido)benzensulfonamid (11) (IC50 = 24,4 μmol L-1), dok je IC50 vrijednost bila 71,8 μmol L-1. Najaktivniji spojevi 9, 10 i 11 evaluirani su kao radiosenzitirajuća sredstva nakon izlaganja spojeva γ-zračenju (8 kGy).

Synthesis of novel pyrazole and pyrimidine derivatives bearing sulfonamide moiety as antitumor and radiosensitizing agents

Several novel pyrazole 10–16 and pyrimidine 17–19 derivatives bearing Sulfonamide moieties were synthesized in order to study their antitumor activity. The synthesized compounds were characterized by elemental analysis, IR, 1H-NMR, and mass spectral data, then screened as antitumor agents against human tumor liver and breast cell lines (HEPG2 and MCF7). All the tested compounds were more potent than the reference drug doxorubicin on human liver (HEPG2) cell line, while on human breast cancer (MCF7) cell line, they were less potent than the reference drug. Additionally, some of the synthesized compounds were evaluated for their ability to enhance the cell killing effect of γ-radiation.

Novel brominated quinoline and pyrimidoquinoline derivatives as potential cytotoxic agents with synergistic effects of γ-radiation

New quinoline derivatives 6, 7 and 19, pyrimidoquinoline derivatives 8–16 and triazolopyrimidoquinoline derivatives 17 and 18 bearing a bromo-substituent were synthesized starting from 3-(4-Bromophenylamino)-5,5-dimethylcyclohex-2-enone 3. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Compounds 9, 11, 17 and 18 showed IC50 values (36.4, 39.7, 39.02 and 36.4 μM, respectively) comparable to that of the reference drug doxorubicin (IC50 = 32.02 μM). On the other hand, compound 6, 14 and 19 exhibited better activity than doxorubicin with IC50 values of 8.5, 23.5 and 23.7 μM. Additionally, the most potent compounds 6, 14 and 19 were evaluated for their ability to enhance the cell killing effect of γ-radiation.

Synthesis of some novel quinolines and pyrimido [4,5-b] quinolines bearing A sulfonamide moiety as potential anticancer and radioprotective agents.

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.