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2019
Hassan, G. S., D. E. Abdel-Rahman, E. A. Abdelmajeed, R. H. Refaey, A. M. Salem, and Y. M. Nissan, "New pyrazole derivatives: Synthesis, anti-inflammatory activity, cycloxygenase inhibition assay and evaluation of mPGES", Eur. J. Med. Chem., vol. 171, pp. 332-342, 2019. Abstract

New pyrazole derivatives 2e5 were synthesized and evaluated for their COX-1 and COX-2 inhibitory activity in vitro. All compounds showed good inhibitory activity at a nanomolar level and most compounds exhibited selectivity towards COX-2 inhibition. Compounds 2a, 3b, 4a, 5b and 5e exhibited IC50 towards COX-2 enzyme of 19.87, 39.43, 61.24, 38.73 and 39.14 nM, respectively. Furthermore, compounds 3b, 4a, 5b and 5e exhibited a selectivity index of 22.21, 14.35, 17.47 and 13.10, respectively. The most active compounds were further subjected to in vivo anti-inflammatory assay. The tested compounds showed better or comparable activity to celecoxib as positive control. In order to explore their binding mode and selectivity behaviour, molecular docking in the active site of COX-2 was carried out for these derivatives. Analysis of the docked poses of the compounds showed that they adopt similar conformations to the highly selective COX-2 inhibitor, SC-558. The docking pose of compound 3b was confirmed by molecular dynamics. All the tested compounds exhibited potent inhibitory effect on the production of PGE2, in addition to their inhibition of COX-2 enzyme.

Amin, K., O. El-Badry, D. Abdel-Rahman, and U. Ammar, "Synthesis and In Vitro Biological Evaluation of New Pyrido[2,3-b]pyrazinone-Based Cytotoxic Agents and Molecular Docking as BRAF Inhibitors", ChemistrySelect, vol. 4, pp. 8882 –8885, 2019. Abstract

In this study, synthesis of new pyrido[2,3-b]pyrazinone derivatives were identified. The in vitro cytotoxic activity of synthesized compounds against human colon cancer cell line (HCT 116) and kinase assay (V600EBRAF) were investigated. The results revealed that compounds 4b and 4c (4-nitro and 4-methoxybenzylidene acid hydrazide substitution, respectively) were the most active compounds among the synthesized derivatives (IC50 12.120 and 13.103 μM, respectively). Moreover, they exhibited inhibitory activity against V600EBRAF (Inh % 79.23 and 81.33, respectively). In addition, the designed derivatives were subjected to be simulated with the active site of mutated BRAF kinase domain using a suitable molecular docking protocol. Docking results coincided with good activity of compound 4c and showed high docking score with BRAF protein kinase domain -21.85171 kcal/mol better than native ligand. The results of this study consider pyridopyrazinone scaffold (with substituted phenyl ring through a spacer) a key nucleus for further molecular and structural optimization.

2017
Hassan, G. S., D. E. Abdel-Rahman, Y. M. Nissan, E. A. Abdelmajeed, and T. M. Abdelghany, "Novel pyrazolopyrimidines: Synthesis, in vitro cytotoxic activity and mechanistic investigation.", Eur. J. Med. Chem., vol. 138, pp. 565 - 576, 2017. Abstract

A series of novel pyrazolo[3,4-d]pyrimidines bearing benzenesulfonamide moiety 5a-f, 6 and 7 were synthesized. Cytotoxic screening was conducted against MCF-7 and HepG2. 6-(4-Methoxyphenyl)-4-oxopyrazolopyrimidine derivative 5e and 4-imino-6-oxopyrazolopyrimidine derivative 6 revealed potent cytotoxic activity with IC50 1.4 µM (MCF-7) and 0.4 µM (HepG2), respectively compared to that of doxorubicin, (IC50 = 1.02 μM and 0.9 μM, respectively). Compounds 5e and 6 were subjected to cell cycle analysis and apoptosis assay after 24h and 48h treatment. Compound 5e arrested cell at G1 phase, while 6 arrested cell at S and G2/M phases, respectively. The apoptotic effect of both compounds were evidenced by pre G1 apoptosis as its percentage increased by time (7.38%, 11.61%) and (13.92%, 16.71%), respectively. Apoptosis induction capability was confirmed by the effect on early and late apoptosis and augmentation of caspase-3 level. Furthermore, compound 6 inhibited CDK2 enzyme with IC50 = 0.19 μM and increased levels of its regulators, P21 and P27 by 10.06% and 8.5%, respectively. Moreover, a molecular docking study of compound 6 on CDK2 enzyme was adopted to explore binding interaction with amino acid residues of its active site.

El-Ansary, S. L., D. E. Abdel-Rahman, and L. M. A. Abdel-Ghany, "Synthesis and Anticancer Evaluation of Some New 3-Benzyl-4,8- Dimethylbenzopyrone Derivatives.", TOMCJ, vol. 11, pp. 81-91, 2017. Abstract

Introduction:
New benzopyrone derivatives such as Schiff’s like compounds, acetohydrazides or substituted with oxadiazole or pyrazole heterocycles were synthesized from parent acid hydrazide compound 3.
Methods and Materials:
Structures of the synthesized compounds were elucidated using IR, NMR and mass spectroscopy. All the synthesized derivatives were selected by National Cancer Institute (NCI), Bethesda, and evaluated for their in vitro anticancer activity in the full NCI 60 cell lines panel assay.
Results and Conclusion:
Schiffs like compounds 4a, b and c were found to have good growth inhibition % against numerous cell lines that belong mainly to leukemia, non-small cell lung, CNS and breast Cancer subpanels.

2016
El-Ansary, S. L., D. E. Abdel-Rahman, and N. M. A. Eldydamony, "Coumarins: Biological activity and SAR studies.", Der Pharma Chemica,, vol. 8, issue 15, pp. 61-74, 2016. Abstract

Over the past decades, literature survey revealed that, many naturally occurring and synthetic coumarin derivatives have been discovered and biologically evaluated for a broad range and diverse biological activities. This review provides a systematic summary and insight of the whole range of medicinal chemistry in the current developments of coumarin compounds and some overview on photochemotharpy, linear (psoralen) and angular (angelicin) furocoumarins and structure-activity relationships are also discussed. The perspectives of the future development of coumarin based medicinal chemistry are also presented.

El-Ansary, S. L., G. S. Hassan, D. E. Abdel-Rahman, N. A. Farag, M. I. Hamed, and M. A. Baset, "Design, synthesis and biological evaluation of some new succinimide, 2-iminothiazoline and oxazine derivatives based benzopyrone as anticonvulsant agents.", Int. J. Pharm. Pharm. Sci., vol. 8, issue 4, pp. 222-228, 2016. Abstract

Objective: The objective of the present study was to synthesize novel benzopyrone derivatives with potential and safer anticonvulsant activity.
Methods: New benzopyrone derivatives have been synthesized and characterized by spectral and elemental analysis. These compounds tested for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens (phase 1), which are the most widely employed seizure models for early identification of new anticonvulsant agents. Phase 2 including, neurotoxicity screening and quantitative determination of the median effective dose (ED50), median lethal dose (LD50) and protective index (PI) for the active compounds from phase 1.
Results: Compound 12b possessed potent anticonvulsant activity with ED50 values of 94.75 and 70.7 mg/kg in the MES and scPTZ screens respectively, and had LD50 value of 2546 mg/kg after intraperitoneal injection to mice, which provide compound 12b with a wide protective index of 26.87 and 36.01 for MES and scPTZ screens respectively compared to the reference drug Phenobarbital with PI of 12.16 and 20.08, respectively. In addition, compound 12b exhibited mild neurotoxicity at the maximum administrated dose (200 mg/kg).
Conclusion: Compound 12b possessed broad spectrum activity for the treatment of all types of seizures, with a wide protective index compared to
Phenobarbital. Consequently, compound 12b can be selected as a new bio candidate lead for further study.

Amin, K. M., O. M. El-Badry, D. E. Abdel-Rahman, U. M. Ammar, and M. M. Abdallah, "Design, synthesis, anticancer evaluation and molecular docking of new V600EBRAF inhibitors derived from pyridopyrazinone.", Eur. J. Chem., vol. 7, issue 1, pp. 19-29 , 2016. Abstract

Design and synthesis of some new pyridopyrazinone derivatives as anti-proliferative agents were described. The cytotoxic activities of the synthesized compounds against melanoma cell line (LOXIMVI), ovarian cell line (OVCAR3), thyroid cell lines (CAL62, FTC133, BCPAP and ML1) and colon cell lines (HT29 and HCT116) were investigated. Results revealed that most compounds were active and compound 3d was the most active one. It exhibited promising activity against all tested cell lines. In addition, in vitro kinase assay against both WTBRAF and V600EBRAF was performed for all synthesized compounds. Furthermore, molecular docking of tested compounds was established with active site of V600EBRAF kinase domain. Results of kinase inhibition assay and molecular docking revealed that, compounds 1, 3d,e,h,I, 5d,e and 6b were potent inhibitors for V600EBRAF kinase enzyme involved in number of cancer types as melanoma, ovarian and thyroid cancer.

2014
Hassan, G. S., D. E. Abdel-Rahman, D. O. Saleh, and G. A. Abdel-Jaleel, "Benzofuran-morpholinomethyl-pyrazoline hybrids as a new class of vasorelaxant agents: Synthesis and QSAR study.", Chem. Pharm. Bull. (Tokyo), vol. 62, issue 12, pp. 1238 - 1251, 2014. Abstract

The benzofuran–morpholinomethyl–pyrazoline hybrids 4a–e, 5a–e and 6a–j were synthesized via reaction of α,β-unsaturated carbonyl compounds 3a–e with hydrazine hydrate, semicarbazide or thiosemicarbazide.Applying the Mannich reaction to 5-(5-aryl-4,5-dihydro-1H-pyrazol-3-yl)-4-methoxybenzofuran-6-ols 7a–e with morpholine hydrochloride and paraformaldehyde afforded positional isomeric 7-morpholinomethyl derivatives 4a–e and N-morpholinomethyl derivatives 8a–e. All the synthesized compounds showed significant vasodilatation properties in isolated thoracic aortic rings of rats precontracted using the standard norepinephrine hydrochloride technique. Compounds 3d, 3e, 5a–c, 6b, 6c, 6f, 6h and 6i exhibited activity (IC50 0.3185–0.4577 mM) superior to that of prazocin (IC50 0.487 mM), while 5d, 6j and 8c showed comparable activity (IC50 0.4789–0.4951 mM). The quantitative structure–activity relationship study revealed a correlation between the observed vasorelaxant activities of the newly synthesized compounds and their different physicochemical parameters, especially solubility, in addition to structure connectivity and energetic quantities calculated from stored three dimensional (3D) conformations. Absorption, distribution, metabolism and elimination (ADME) evaluation showed good agreement with the biological results obtained.

El-Ansary, S. L., M. M. Hussein, D. E. Abdel-Rahman, and M. I. A. - L. Hamed, "New furobenzopyrones: Synthesis, antimicrobial and photochemotherapeutic evaluation, QSAR and molecular docking studies.", Der Pharma Chemica, vol. 6, issue 6, pp. 169 -191, 2014. Abstract

The synthesis of some new linear furobenzopyrone 3a-h, 7a,b and angular furobenzopyrone derivatives 9a-s and 12a,b were described on the base of being monofunctional compounds to decrease possible toxicity. All the prepared compounds were evaluated for their antimicrobial and photosensitizing activities. Compounds 2e, 4 and 7b were found to have good antimicrobial activity while only compound 2e exhibited higher photosensitizing activity than xanthotoxin. In addition, photosensitizing activity increased upon increasing time of radiation and concentration of substance. Quantitative structure–activity relationship (QSAR) study was applied to find a correlation between the photosensitizing activities of the newly synthesized furobenzopyrone derivatives and their physicochemical parameter. Furthermore, docking study was undertaken to gain insight into the possible binding mode of these compounds with the binding site of the DNA gyrase (topoisomerase II) enzyme which is responsible for resolving topological problems which arise during the various processes of DNA.

Amin, K. M., N. M. Abdel-Gawad, D. E. Abdel-Rahman, and M. E. K. M. Ashry, "New series of 6-substituted coumarin derivatives as effective factor Xa inhibitors: Synthesis, in vivo antithrombotic evaluation and molecular docking", Bioorg. Chem., vol. 52, pp. 31 - 43, 2014. Abstract

Despite recent progress in antithrombotic therapy, there’s still an unmet medical need for safe and orally available anticoagulants. Encouraged by the marked antithrombotic and anticoagulant activities of some coumarin derivatives, twenty-three new N-coumarinyl-4-amidinobenzamides 4a–f and 6-heterocycle substituted coumarin derivatives 5, 6a,b, 10a–e, 12a–e and 14a–d were synthesized and evaluated for their in vivo antithrombotic activity. The most active congeners were the unsubstituted amidine 4a (36.5 s), coumarinyl oxadiazole 5 (42.3 s), bis coumarinyl oxadiazole 6b (37.8 s) and coumarinyl pyrazole 10b (38.5 s) that presented prothrombin time (PT) values comparable to the reference drug warfarin (42.3 s). Furthermore, docking studies were undertaken to gain insight into the possible binding mode of these compounds with the coagulation factor Xa (FXa) binding site.

Abdel-Rahman, D. E., and K. O. Mohamed, "Synthesis of novel 1,3,4-thiadiazole analogues with expected anticancer activity", Der Pharma Chemica, vol. 6, issue 1, pp. 323 - 335, 2014. Abstract

Synthesis of substituted imidazo[2,1-b]-1,3,4-thiadiazoles 2a,b-6, substituted 1,3,4-thiadiazolo[3,2-a]pyrimidines 7-9 and 1,3-disubstituted thioureas 10a-e was reported. Structures of all synthesized compounds were elucidated using IR, NMR and mass spectroscopy. All the prepared derivatives were evaluated for their cytotoxic activity against tumor cell line A549 (Non-Small Cell Lung Cancer Cell Line) using Sulfo-Rodamine B (SRB) standard method. Most of the tested compounds exhibited potent cytotoxicity especially compounds 4, 5, 8 and 10b-d (IC50 2.58-6.47 μM). In order to find a molecular target for newly synthesized compounds, docking study was performed to explore the possible binding mode of these compounds with the binding site of fibroblast stromelysin-1 enzyme, which is involved in several pathological conditions including cancer.

El-Ansary, S. L., D. E. Abdel-Rahman, and A. H. Abdel-Haleem, "Synthesis, antimicrobial, photochemotherapeutic evaluation and molecular docking of novel furobenzopyrones, tetrahydrobenzo- and benzofurobenzopyrones.", Der Pharma Chemica, vol. 6, issue 6, pp. 256 - 272, 2014. Abstract

New series of tricyclic compounds (linear furobenzopyrones 3a-d and angular furobenzopyrones 11a-h) and tetracyclic compounds (tetrahydrobenzofurobenzopyrone 5a,b and benzofurobenzopyrone 6a,b) derivatives were synthesized to ensure mono functional photoreaction with DNA in order to decrease toxicity. All prepared compounds were evaluated for antimicrobial and photochemotherapeutic activities. Compounds 2d, 3d, 5a, 10c and 11d were found to have good antimicrobial activity while only compound 11e exhibited good photosensitizing activity. In addition, molecular docking study was applied to elucidate a molecular target for the antimicrobial activity and gain insight into the possible binding mode of these compounds with the active site of the DNA gyrase.

El-Ansary, S. L., M. M. Hussein, D. E. Abdel-Rahman, and L. M. A. Abdel-Ghany, "Synthesis, docking and in vitro anticancer evaluation of some new benzopyrone derivatives", Bioorg. Chem., vol. 53, pp. 50 - 66, 2014. Abstract

The synthesis of some new 3-alkyl-7-hydroxy-4-methyl-8-substituted-1H-benzopyran-2-ones, 6-alkyl-7-methyl-2-substituted amino-5H-pyrano[6,5-e] benzoxazol-5-ones, 7-alkyl-8-methyl-3-substituted-2,6-dihydropyrano[6,5-f]-1,4-benzoxazin-6-ones, 7,8-disubstituted-3-ethyl-4-methyl-1H-benzopyran-2-ones and 3-alkyl-4-methyl-7-substituted-1H-benzopyran-2-ones were described. Fourteen compounds were selected by National Cancer Institute (NCI), Bethesda, and evaluated for their in vitro anticancer activity in the full NCI 60 cell lines panel assay by a single dose test. Compounds 4a, 18a, 18b and 23a were found to be broad-spectrum antitumors showing effectiveness toward numerous cell lines that belong to different tumor subpanels. Furthermore, docking studies were undertaken to gain insight into the possible binding mode of these compounds with the binding site of the casein kinase II (CK2) enzyme which is involved in cell survival and proliferation through a number of downstream effectors.

2013
Hassan, G. S., and D. E. Abdel-Rahman, "Synthesis and biological evaluation of some substituted-2-N-(5-chloro-2-methoxy-4-methylphenylsulphonyl) glutamic acid derivatives against prostate cancer cell line PC3", Chem. Pharm. Bull. (Tokyo), vol. 61, issue 2, pp. 212 - 221, 2013. Abstract

New series of substituted glutamine 5a–l and glutamic acid diamides, diureide and dihydrazide 7a–e were synthesized from parent glutamic acid compound 3 and evaluated for their cytotoxic activity against tumor cell line PC3 (prostate cancer cell line). Most of the tested compounds exploited potent growth inhibitory activity with IC50 values ranging 0.034–3.97 μm. Particularly, compounds 5a, 3, 5j, 5b, 7c, 7e, 5l, and 5k exhibited superior potency (IC50=0.034, 0.04, 0.05, 0.074, 0.25, 0.4, 0.49, 0.522 μm, respectively) to the reference drug Doxorubicin (IC50=0.63 μm), while compound 7b showed IC50, 0.71 μm, comparable to that of Doxorubicin. In summary, the newly synthesized compounds provided promising new lead for the future design and development of glutamine and glutamic acid derivatives as novel antitumor agents. The quantitative structure–activity relationship (QSAR) study was applied to find a mathematical correlation between the structures of compounds and their activity against PC3 cell line expressed as IC50 values.

Abdel-Rahman, D. E., "Synthesis, Quantitative Structure–Activity relationship and biological evaluation of 1,3,4-oxadiazole derivatives possessing diphenylamine moiety as potential anticancer agents", Chem. Pharm. Bull. (Tokyo), vol. 61, issue 2, pp. 151 - 159, 2013. Abstract

Synthesis of 2,5-disubstituted-1,3,4-oxadiazole (2a–c), 3-substituted aminomethyl-5-substituted-1,3,4-oxadiazole-2(3H)-thione (4a–m) and 2-substituted thio-5-substituted-1,3,4-oxadiazole (5a, b) had been described. All the synthesized derivatives were screened for anticancer activity against HT29 and MCF7 cancer cell lines using Sulfo-Rodamine B (SRB) standard method. Most of the tested compounds exploited potent antiproliferative activity against HT29 cancer cell line rather than MCF7 cancer cell line. Compounds 2a–c, 4f and 5a exhibited potent cytotoxicity (IC50 1.3–2.0 μm) and selectivity against HT29 cancer cell line. Quantitative structure–activity relationship (QSAR) study was applied to find a correlation between the experimental antiproliferative activities of the newly synthesized oxadiazole derivatives with their physicochemical parameter and topological index.

2012
El-Ansary, S. L., M. M. Hussein, D. E. Abdel-Rahman, and M. I. A. - L. Hamed, "Synthesis and docking studies of furobenzopyrones of potential antimicrobial and photochemotherapeutic activities", Life Sci. J.,, vol. 9, issue 4, pp. 1114 - 1125, 2012. Abstract

Benzopyrone and furobenzopyrone derivatives were designed to be synthesized and screened for antimicrobial and photosensitizing activities. Synthesis of benzopyrone derivatives (IVa-e and Va-d) was proceeded via etherification of hydroxy benzopyrone I and II with -bromoacetophenone derivatives IIIa-e followed by cyclization to achieve linear furobenzopyrone analogues (IVa-e and Va-d). Surprisingly, an angular furobenzopyrone derivative VIII instead of the linear analogue was synthesized in one step reaction from the condensation of hydroxyl benzopyrone II with 3,4-dimethoxy--bromoacetophenone IIIe. This may be attributed to the presence of the two methoxy substituents which are electron donating group. All newly synthesized compounds were evaluated for their antimicrobial and photosensitizing activities by the paper disc diffusion method compared with xanthotoxin. Results showed that, compounds IVd, IVe, Vd, VIIa and VIII possessed antimicrobial and potential photosensitizing activity. Compounds IVe and VIII exhibited antimicrobial activity higher than that of xanthotoxin while the other three compounds were less active than xanthotoxin. Docking of the antimicrobial active compounds into topoisomerase II using MOE program was performed in order to predict the correlation between dock scores and antimicrobial activity of these compounds.

2008
Abdel-Rahman, D. E., "Synthesis and evaluation of some new 1,2,4-triazole derivatives as antitumor agents", Az. J. Pharm. Sci., vol. 37, pp. 49 - 63, 2008. Abstract

New 3,4,5-trisubstituted 1,2,4-triazole, 3,6-disubstituted triazolothiadiazole, 3,6-disubstituted and 3,6,7-trisubstituted triazolothiadiazine compounds were synthesized and their structures were confirmed on the basis of IR, 1HNMR, Mass spectral data and micro analyses. All prepared compounds were tested for anticancer activity against MCF7 (Breast carcinoma cell line). All tested compounds exhibited promising activity where IC50 ranged from 0.47-6.44 μg and IC10 for compounds 8c, 8e, 10, 11a, 11b, 12, 13, 14 and 17 ranged from 4.83-10 μg.

Amin, K. M., D. E. Abdel-Rahman, and Y. A. Al-Eryani, "Synthesis and preliminary evaluation of some substituted coumarins as anticonvulsant agents", Bioorg. Med. Chem., vol. 16, issue 10, pp. 5377 - 5388, 2008. Abstract

Some new substituted coumarinylthiazolines, coumarinylthiazolidin-4-ones, and substituted chromenothiazoles were synthesized and evaluated for anticonvulsant activity. Some selected compounds were assayed against seizures induced by pentylenetetrazole (PTZ) and strychnine in mice. Compounds 3b, 6b, and 7b were the most active of the series against PTZ induced seizures. Compound 7b provided anticonvulsant activity (PD50 = 95 mg/kg, ip) at a dose 200 mg/kg compared to phenobarbital (PD50 = 16 mg/kg, ip) at a dose 30 mg/kg (90% protection). No clear correlation was observed between the antiepileptic activity and molecular lipophilicity descriptors of the tested compounds.

2007
El-Moghazy-Aly, S. M., D. E. Abdel-Rahman, S. E. - S. Abbas, M. A. - A. Mohammed, and A. H. Amin, "Design and synthesis of some substituted acridine derivatives of anticipated antitumor activity", Bull. Pharm. Sci. Assiut Univ., vol. 30, issue 2, pp. 213 - 234, 2007. Abstract

Four series of new acridine derivatives of anticipated antitumor activity have been designed and synthesized. The first series belongs to 4-substituted phenylhydrazinocarbonylmethyl 9-oxo-9,10-dihydroacridine-4-carboxylate 10a-h. The second series consists of phenylhydrazinocarbonylmethyl 9-(4-substituted phenyl)aminoacridine-4-carboxylate 12a-k, while the third series comprises 4-substituted phenylcarbamoylmethyl 9-(4-substituted phenyl)aminoacridine-4-carboxylate 15a-k. The fourth one belongs to phenylcarbamoylmethyl 9-(4-substituted phenyl)aminoacridine-4-carboxylate 17a-j. The chemical structure of synthesized compounds was elucidated by spectral data and elemental analysis. Seventeen selected compounds (10a, 10g, 10h, 12a, 12d, 12g, 12h, 12k, 15a, 15c, 15g, 15h, 15k, 17a, 17f, 17g and 17j) were tested against breast cancer cell line (MCF7) and eight compounds (12g, 12h, 12k, 15g, 15h, 17f, 17g, 17j) were found to exhibit significant antitumor activity.

Abdel-Rahman, D. E., N. A. I. Mansour, and H. A. A. Latif, "Synthesis of some novel quinazolin-4(3H)-one derivatives with anticipated anti-inflammatory activity", Az. J. Pharm. Sci., vol. 36, pp. 79 - 92, 2007. Abstract

Novel series of 2-benzamido-N′-(6-iodo-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)-3-substituted phenylacrylohydrazide 6a-e, 7-iodo-4-phenyl-1-substituted amino[1,2,4] triazolo[4,3-a]quinazolin-5(4H)-one 7a,b, 2-(2-(un)substituted arylidenehydrazinyl)-6-iodo-3-phenylquinazolin-4(3H)-one 8a-e, 7-iodo-4-phenyl-1-(un)substituted aryl-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)one 9a-e, 2-(2-(un)substituted arylmethyl-hydrazinyl)-6-iodo-3-phenylquinazolin-4(3H)-one 10a-e and 6-iodo-2-(4-oxo-2-(un)substituted phenylthiazolidin-3-ylamino)-3-phenylquinazolin-4(3H)-one 11a,b were synthesized. The chemical structure of synthesized compounds was elucidated by spectral data and elemental analyses. Sixteen selected compounds (6a, 6b, 6c, 7a, 8a, 8b, 8c, 8e, 9a, 9b, 9c, 10a, 10b, 10c, 11a and 11b) were screened for anti-inflammatory activity. Only compounds 10a and 11b exhibited appreciable anti-inflammatory activity compared with diclofenac sodium.

El-Moghazy-Aly, S. M., N. M. Abdel-Gawad, D. E. Abdel-Rahman, and J. H. Abdullah, "Synthesis of some substituted acridine derivatives of anticipated antitumor activity", Bull. Fac. Pharm. Cairo Univ., vol. 45, issue 3, pp. 129 - 143, 2007. Abstract

Four series of new acridine derivatives were synthesized and tested for antitumor activity. The first series consists of 4-[3-(9-oxo-9,10-dihydroacridin-2-yl)-1-triazenyl]benzenesulfonamide derivatives 6a-i. The second one consists of 4-[3-(9-oxo-9,10-dihydroacridin-3-yl)-1-triazenyl]benzenesulfonamide derivatives 7a-i, while third series belongs to 4-[3-(9-oxo-9,10-dihydroacridin-4-yl)-1-triazenyl]benzenesulfonamide derivatives 8a-i, and the fourth one comprises 4-[3-(acridin-9-yl)-1-triazenyl]benzenesulfonamide derivatives 14a-i. The chemical structure of synthesized compounds was elucidated by spectral data and elemental analysis. Seventeen selected compounds 6a, 6e, 6f, 6i, 7a, 7e, 7f, 7i, 8a, 8e, 8f, 8g, 8i, 14a, 14e, 14f and 14i were tested against breast cancer cell line (MCF7) at National Cancer Institute, Cairo University. Results revealed that most of the tested compounds exhibited significant antitumor activity except compounds 7a and 8g.

2006
Abadi, A. H., S. M. Abou-Seri, D. E. Abdel-Rahman, C. Klein, O. Lozach, and L. Meijer, Synthesis of 3-substituted-2-oxindole analogues and their evaluation as kinase inhibitors, anticancer and antiangiogenic agents, , 2006. Abstract

Several analogues of the 3-substituted-2-oxoindole chemotype were synthesized by condensing isatin or the appropriate haloisatin with some amino acids or histamine under neutral conditions. All the imino derivatives produced were tested for kinase inhibitory properties against three serine/threonine kinases, namely CDK1/cyclin B, CDK5/p25 and GSK3α/β. Most of the histidine derivatives showed inhibitory properties to the three kinases in the low micromolar range. The histamine derivatives were less potent against CDK1/cyclin B and CDK5/p25 and totally inactive against GSK3α/β. So, the management of the carboxyl function may be a tool to impart selectivity in such family of kinases. Docking of 2-{[-5-bromo-2-oxoindolin-3-ylidene]amino}-3-(1H-imidazol-2-yl)propanoic acid 14 to CDK5/p25 indicates that this compound can interact with the enzyme through four hydrogen bonds; for GSK/3β, the ligand poses itself in another orientation, also four hydrogen bonds can be formed between the ligand and the receptor, otherwise hydrophobic interactions seem to predominate. Also, all the final compounds were tested for their in vitro antitumor properties against MCF7 (breast), NCI-H460 (lung) and SF268 (CNS) cancer cell lines. None of the synthesized compounds was cytotoxic at 10–4 molar concentration. Moreover, compounds 13 and 14 were tested for potential antiangiogenic properties by testing their ability to inhibit the proliferation of human umbilical vein endothelial cells (HUVECs), cord formation and migration in response to chemoattractant. Only compound 14 showed moderate inhibitory properties to HUVECs proliferation and cord formation while its non-brominated derivative 13 did not. Thus, the antiangiogenesis properties are not apparently caused by inhibition of any of the tested kinases.

2002
El-Moghazy-Aly, S. M., A. N. Mikhael, A. E. - S. Farag, and D. E. Abdel-Rahman, "Synthesis, molecular modeling and antitumor activity of some substituted acridine derivatives", Egypt. J. Pharm. Sci., vol. 43, issue 1 - 2, pp. 29 - 51, 2002. Abstract

9 Series of new acridine derivatives of anticipated antineoplastic activity have been synthesized. The first series consists of N,N′-1,2-bis[9-(4-substituted sulfamoylphenyl) aminoacridine-4-carboxamide] ethylenediamine. The second comprises of N,N′-1,2-bis[9-(4-substituted sulfamoylphenyl) aminoacridine-4-carboxamide] phenylenediamine. The third and fourth are 1-(4-substituted sulfamoylphenyl) aminoacridine-4-carboxylic acid (4-substituted sulfamoylphenyl) amide. The fifth and sixth are 9-oxo-1-(4-substituted aminosulfamoylphenyl)-9,10-dihydroacridine-4- carboxylic acid (4-substituted sulfamoylphenyl) amide. The seventh is 2-substituted phenyl-2,6-dihydropyrazolo[3,4,5-kl]acridine-5-carboxylic acid (4-substituted sulfamoylphenyl) amide. The eighth is 4-{5-(N′-phenylhydrazinocarbonyl)-6H-pyrazolo[3,4,5-kl]acridine-2-yl}-N-substituted benzenesulfonamide. The last one belongs to 2-substituted phenyl-2,6-dihydropyrazolo[3,4,5-kl]acridine-5-carboxylic acid (4-substituted sulfamoylphenyl) hydrazide.

1998
El-Moghazy-Aly, S. M., M. M. Hussein, D. E. Abdel-Rahman, and G. M. El-Taliawi, "Synthesis and antitumor activity of some hydrazinoacridine, hydrazinoacridonanil and 9-oxo-9,10-dihydroacridine-4-carboxazide Derivative", Bull. Fac. Pharm. Cairo Univ., vol. 36, issue 3, pp. 57 - 64, 1998. Abstract

Six series of acridine derivatives of anticipated antitumor activity have been designed and synthesized. 9 Series of new acridine derivatives of anticipated antineoplastic activity have been synthesized. The first comprises of 9-(4-substituted sulfamoylphenyl) hydrazinoacridine. The second consists of 9-(4-substituted sulfamoylphenyl) hydrazinoacridoneanil. The third includes N-substituted-9-(4-substituted sulfamoylphenyl) hydrazinoacridine-4-yl-[N-substituted(4-substituted sulfamoylphenyl) carboxamide while fourth and fifth includes N-substituted-9-(4-substituted sulfamoylphenyl) hydrazinoacridine-4-yl-[N-substituted(4-substituted sulfamoylphenyl) carboxazide derivatives and sixth includes 9-oxo-9,10-dihydroacridine-4-yl-[N-substituted(4-substituted sulfamoylphenyl) carboxazide derivatives. The rationale behind the synthesis of these compounds, their methods of synthesis as well as the antitumor activities have been presented.

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