Basic Informations

C.V

Curriculum vitae (C.V) 1) Personal data: John Nafea Philoppes Soliman Name: Tanta-Elgharbia Place of birth: 3-12-1978 Date of birth: Egyptian Nationality : Arabic & English Language : Pharmaceutical Science General specialization: Pharmaceutical Organic Chemistry Accurate specialization: John_philoppes@yahoo.com E-mail:? 2) Scientific qualification: Country Affiliation Faculty General specification Date Degree Egypt Beni-Suef University Pharmacy Organic Chemistry 2014 Ph.D Egypt Cairo University, Beni-Suef branch Pharmacy Organic Chemistry 2008 M. Sc. Egypt Cairo University, Beni-Suef branch Pharmacy Pharmaceutical Sciences 2000 B. Sc. 3) Chronology of Employment: Country Affiliation The end of employment The start of employment Academic degree Job Egypt Faculty of Pharmacy, Cairo University, Beni-Suef branch 2-2008 2000 B. Sc. Demonstrator of Pharmaceutical Organic Chemistry Egypt Faculty of Pharmacy, Beni-Suef University 6-2014 2008 M. Sc. Assistant Lecturer of Pharmaceutical Organic Chemistry Egypt Faculty of Pharmacy, Beni-Suef University Till now 2014 PhD Lecturer of Pharmaceutical Organic Chemistry 4) Courses and workshops: Year place Nature of course/ workshop Name of course 2009 Ministry of Communications and Information Technology Training Course ICDL 1 2011 Faculty of Pharmacy, Beni-Suef University Conference Recent Advances in Pharmaceutical Research 2 2014 Beni-Suef University Training Course TOEFL 3 2014 Beni-Suef University Workshop Recent Advances in Chemistry and Biology of Natural Products 4 2014 Beni-Suef University Training Course International and Local MOU in Beni-Suef University and Ways to Activate 5 2014 National Research Center Cairo-Egypt International Conference 5th International conference on advances in chemistry and applied chemistry (ICACAC-5) 6 2014 Faculty of Pharmacy, Beni-Suef University Training Course Specifications of courses and programs 7 2014 Beni-Suef University Training Course Encouragement of patent registrations: specifications and evaluations 8 2015 Beni-Suef University Symposium Scientific Awards: Types and how to obtain it. 9 2015 Faculty of Pharmacy - Beni-Suef University Conference 1st International Conference on Health between Nutrition and Treatment 10 2016 Faculty of Pharmacy- Beni-Suef University Workshop Academic standards that meet the requirements of the graduate 11 2016 Faculty of Pharmacy Beni-Suef University Workshop Assessing and evaluating students' methods 12 2016 Huston, USA Video presentation in International Conference International Conference on Applied Chemistry 13 2017 Faculty of Pharmacy- Beni-Suef University Workshop Updating Course Specification- 1st Part 14 2017 Faculty of Pharmacy- Beni-Suef University Workshop Updating Course Specification- 2nd Part 15 2018 Beni-suef university Training Course The Credit Hour System 16 2018 Beni-suef university Training Course Competitive Research Projects 17 2018 Beni-suef university Training Course Research Team Management 18 2018 Beni-suef university Training Course Integrity, transparency and anti-corruption 19 2018 Beni-suef university Training Course Time and Meeting Management 20 2018 Beni-suef university Training Course Organizing Scientific Coferences 21 2019 Nahda University Conference NUB 2nd Conference of Scientific Research in Pharmacy " Future Insight" 22 5) The administrative positions: Place End of service Start of service Academic degree Job Facuty of Pharmacy, Beni-Suef University 2016 2015 Lecturer Member of community and environmental committee Facuty of Pharmacy, Beni-Suef University Till now 2014 Lecturer Coordinator of the Scientific Research Committee of the Quality Assurance Unit Facuty of Pharmacy, Beni-Suef University 2017 2016 Lecturer Student Communication Officer 6) The scientific production: A- Scientific dissertation:- Date Faculty / Department Donator university Title of thesis Scientific dissertation 2-2008 Pharmaceutical Organic Chemistry Department, Facuty of Pharmacy Faculty of Pharmacy, Cairo University, Beni-Suef branch Synthesis of certain Heterocyclic Compounds Chemically related to Anti TB Drugs Master 5-2015 Pharmaceutical Organic Chemistry Department, Facuty of Pharmacy Beni-Suef University Synthesis of Substituted Benzothiazole and Benzoxazole derivatives of Antitumor Activity PhD B-Published Papers:- Publication data Name of journal Author/s Title volume Year 5 2013 Journal of Chemical and Pharmaceutical Research Manal M. Kandeel, Eman K. A., Mohammed A.A., John N. Philoppes Synthesis and in vitro antitumor activity of new benzothiazole and benzoxazole derivatives Vol. 20, 16620-16642 2015 Molecules Phoebe F. Lamie, John N. Philoppes, Lucie Rarova and Jiri Gruz Design, Synthesis and Evaluation of Novel Phthalimide Derivatives as in Vitro Anti-Microbial, Anti-Oxidant and Anti-Inflammatory Agents. (v) 210-224 2016 ARKIcVOC Eman K. A. Abdelall and John N. Philoppes Synthesis and cytotoxic activity of new pyrazolo[1,5- a]pyrimidines and determination of pyrimidine regiospecific ring formation with 2D NMR DOI: 10.1007/s00044-017-1839-4 2017 Medicinal Chemistry Research John N. Philoppes, Phoebe F. Lamie, Design and synthesis of three series of novel antitumor–azo derivatives VOL. 32, NO. 1, 805–820 2017 Journal of Enzyme Inhibition and Medicinal Chemistry Phoebe F. Lamie, John N. Philoppes, Amany A. Azouz & Nesreen M. Safwat Novel tetrazole and cyanamide derivatives as inhibitors of cyclooxygenase-2 enzyme: design, synthesis, anti-inflammatory evaluation, ulcerogenic liability and docking study 76 , 67-80 2018 Bioorganic Chemistry Madlen B. Labib, John N. Philoppes, Phoebe F. Lamie, Esam R. Ahmed Azole-hydrazone derivatives: Design, synthesis, in vitro-biological evaluation, dual EGFR/HER2 inhibitory activity, cell cycle analysis and molecular docking study as anticancer agents. 351, el700311 2018 Arch Pharm Chem. Life Sci. Phoebe F. Lamie, John N. Philoppes , Lucie Rárová. Design, synthesis, and biological evaluation of novel 1,2-diaryl-4-substituted-benzylidene-5(4H)-imidazolone derivatives as cytotoxic agents and COX-2/LOX inhibitors. 89, doi: https://doi.org/ 10.1016/j.bioorg. 2019.102978. 2019 Bioorganic Chemistry John N. Philoppes, P.F. Lamie Design and synthesis of new benzoxazole/benzothiazole-phthalimide hybrids as antitumor-apoptotic agents 7. Academic experiences: A- Dissertation supervision: Accurate specialization Kind of responsibility The year of permission The Year of registration place Degree Title of dissertation Pharmaceutical Organic Chemistry Supervisor ----- 24/5/2016 Faculty of Pharmacy, Beni Suef University Ph.D. " Synthesis of some new heterocyclic compounds of biological activity" Pharmaceutical Organic Chemistry Supervisor ----- 13/8/2018 Faculty of Pharmacy, Beni Suef University Master " Design and synthesis of new heterocyclic compounds acting as anti-inflammatory agents " B) Teached courses: Accurate specialization University Faculty Grade Language Course name Pharmaceutical Organic Chemistry Beni-Suef Faculty of Pharmacy Under graduate English Pharmaceutical Organic – 1 Pharmaceutical Organic Chemistry Beni-Suef Faculty of Pharmacy Under graduate English Pharmaceutical Organic – 2 Pharmaceutical Organic Chemistry Beni-Suef Faculty of Pharmacy Under graduate English Pharmaceutical Organic – 3 Pharmaceutical Organic Chemistry Beni-Suef Faculty of Pharmacy Under graduate English Pharmaceutical Organic – 4 Pharmaceutical Organic Chemistry Beni-Suef Faculty of Pharmacy Under graduate English Mathematics Pharmaceutical Organic Chemistry Beni-Suef Faculty of Pharmacy Under graduate English Pharmaceutical Organic – 1 clinic Pharmaceutical Organic Chemistry Beni-Suef Faculty of Pharmacy Under graduate English Pharmaceutical Organic – 2 clinic Pharmaceutical Organic Chemistry Beni-Suef Faculty of Pharmacy Under graduate English Pharmaceutical Organic – 3 clinic Pharmaceutical Organic Chemistry Beni-Suef Faculty of Pharmacy Under graduate English Mathematics- clinic Pharmaceutical Organic Chemistry Beni-Suef Faculty of Pharmacy Post graduate English Medicinal Chemistry C- Seminar and meetings: participation without work paper: Year Place Sponsor Conference title 2011 Faculty of Pharmacy, Ben- Suef University Faculty of Pharmacy, Beni-Suef University Recent Advances in pharmaceutical research 2014 National Research Center, Cairo-Egypt National Research Center 5th International conference on advances in chemistry and applied chemistry (ICACAC-5) 2015 Faculty of Pharmacy - Beni-Suef University Faculty of Pharmacy - Beni-Suef University 1st International Conference on Health between Nutrition and Treatment 2019 Faculty of Pharmacy -Nahda University Nahda University NUB 2nd Conference of Scientific Research in Pharmacy " Future Insight" D- Seminar and meetings: participation with work paper: Year Shared with Place Sponsor Conference title 2016 Video presentation Houston, USA Houston, USA International Conference of Applied Chemistry ??? ???? ????? ?????? ???? ???? ???????? ??????? ???????? ???? ??????? – ????? ??? ????

Master Title

Synthesis of Certain Heterocyclic Compounds Chemically Related to Antituberculous Drugs.

Master Abstract

The present thesis comprises a survey covering antimycobacterial drugs with known and unknown mode of action. The study involves the synthesis of ethyl benzothiazole-2-carboxylate (I). Hydrazinolysis of the ester I resulted in the hydrazide II. Condensation of the latter with some aromatic aldehydes afforded the arylidene derivatives IIIa-d. Cyclization of IIIa-d with acetic anhydride yielded substituted 1,3,4-oxadiazoles IVa-d. Also, reaction of the hydrazide II with isatin and certain acid anhydrides led to substituted indolin-3-ylidene V and amide derivatives VI & VII respectively. The investigation also involves the reaction of o-phenylenediamine with succinic anhydride to give 2-aminophenylamidosuccinic acid (VIII) which, on boiling under reflux for 3 hours in absolute ethanol, gave 3-(1H-benzimidazol-2-yl) propanoic acid (IX). Esterification with ethanol led to the corresponding ethyl ester X which upon reaction with hydrazine gave the hydrazide XI. Condensation of the latter with isatin led to indolin-3-ylidene derivative XII. Also, cyclization of the hydrazide XI with some aromatic acids afforded 2,5-disubstitued-1,3,4-oxadiazoles XIIIa-c. Cyclization of the hydrazide XI with acetylacetone yielded compound XIV. Moreover, 3-(1H-benzimidazol-2-yl) propanoic acid hydrazide (XI) was reacted with some aromatic aldehydes yielding arylidene derivatives XVa-e, which upon cyclization with acetic anhydride yielded substituted-1,3,4-oxadiazoles XVIa-d. In addition, reaction of the hydrazide XI with certain acid anhydrides led to substituted amide derivatives XVII & XVIII. On the other hand, ethyl (and/or phenyl) thiosemicarbazides XIXa&b were synthesized via reaction of the hydrazide XI with the corresponding isothiocyanate. The substituted thiosemicarbazides were then cyclized in presence of conc. H2SO4 to give 2,5-disubstituted-1,3,4-thiadiazol derivatives XXa&b, while cyclization of these substituted thiosemicarbazides in the presence of piperidine/H2O led to 1,2,4-triazoles XXIa&b which, upon alkylation with different alkyl and/or aryl halides, gave XXIIa-f. While cyclizayion of ethyl(and/or phenyl) thiosemicarbazides XIXa&b with chloroacetic acid afforded thiazolidinone derivatives XXIIIa&b. 5-Substituted-1,3,4-oxadiazole-2-thiol XXIV was prepared by heating the hydrazide XI with CS2 in the presence of alcoholic KOH. Alkylation of XXIV with different alkyl or aryl halides gave XVa-c. When XXIV was subjected to Mannich reaction conditions, by reacting it with formaldehyde and different secondary amines in ethanol, it gave the corresponding 3-substituted aminomethyl-5-substituted-1,3,4-oxadiazole-2-thiones XXVIa-e.

PHD Title

Synthesis of substituted benzothiazole and benzoxazole derivatives of antitumor activity

PHD Abstract

This thesis comprises four chapters: the first one is an introduction which consists of a brief survey about different routes to synthesize 2-substituted benzothiazoles and 2-substituted benzoxazoles in addition to an account on their cytotoxic activities. The second chapter deals with the aim of the work and the Schemes for the preparation of starting materials and the target benzothiazole, benzoxazole, pyrazole, pyrimidine, quinazoline and benzotriazine containing compounds. The third chapter clarifies the theoretical discussion of the experimental work for the preparation of the starting materials Ia&b and Va&b. Reaction of Ia&b with triethyl orthoformate and malononitrile afforded the key intermediates IIa&b which upon cyclization with hydrazine hydrate yielded IIIa&b. In addition, compound IIa was cyclised to give IVa&b through treatment with certain isothiocyanates. Moreover, substitution of iodide in Va&b by a cyanide anion gave VIa&b from which VIIa&b, VIII and IXa&b were obtained using different acylating agents such as acetic anhydride, p-chlorobenzoyl chloride and chloroacetyl chloride, sequentially. As an extension, nucleophilic substitution of chloro derivatives of IXa&b with different primary and/or secondary amines yielded Xa-d. Furthermore, hydrolysis of the cyano compounds VIa&b either in basic or acidic medium afforded the carboxylic acids XIa&b and the carboxamides XIIa&b, respectively. Formation of quinazoline ring was constructed by reacting VIa&b with different reagents like phenyl isothiocyanate, formamide and formic acid to obtain XIIIa&b, XIVa&b and XVa&b, in the same order. Reaction of XVa&b with phosphorous oxychloride formed the chloro derivatives XVIa&b, which was subjected to nucleophilic substitution reaction by treatment with aromatic amines affording XVIIa-c. On the other hand, alkylation on pyrimidine nitrogen of XVa&b with different alkyl halides achieved XVIIIa&b. A variety of quinazoline derivatives XIXa&b, XXa-d and XXIa-d were formed via reacting XIIa&b with carbon disulfide, aromatic aldehydes and certain isothiocyanates, respectively. Additionally, refluxing compounds XIIa&b in acetic anhydride led to preparation of both oxazinone derivatives XXIIa&b and pyrimidinone derivatives XXIIIa&b. Moreover, reacting compounds XIIa&b with cyclopentanone and cyclohexanone afforded XXIVa-d. Finally, formation of benzotriazine derivatives XXVa&b was obtained by subjecting XIIa&b to a diazotization condition. The structure elucidation of the new compounds was supported by element analysis, IR, 1H NMR in addition to mass spectra. Additionally, a brief account on the docking study was explained through the binding conformations in comparison with the cytotoxic activity. The fourth chapter consists of the experimental part of this work which contains the detailed procedures used for the synthesis of the starting materials Ia&b and Va&b, the intermedtiates IIa&b,VIa&b, IXa&b, XIIa&b, XVa&b and XVIa&b, in addition to the target final compounds IIIa&b, IVa&b, VIIa&b, VIII, Xa-d, XIa&b, XIIIa&b, XIVa&b, XVIIa-c, XVIIIa&b, XIXa&b, XXa-d, XXIa-d, XXIIa&b, XXIIIa&b, XXIVa-d and XXVa&b. This chapter also includes the in-vitro anticancer activity of twenty-six compounds of newly synthesized derivatives compared to Ib as a standard and demonstrates the correlation between the results of the molecular docking study and anticancer evaluation. There was some sort of constancy between the docking study prediction and the in-vitro biological cytotoxic evaluation. Compound XVIIc showed the highest energy score (-21.34 Kcal/mol) and exhibited the most potent in-vitro cytotoxic activity with IC50 equal to 0.009 µM, while compounds XIa and XXIVa showed intermediate energy scores (-16.79 to -15.75 Kcal/mol) and exhibited moderate in-vitro cytotoxic activity with IC50 0.066 and 0.067 µM, respectively. On the other hand, XXVa showed a weak energy score -15.46 and exhibited the least in-vitro cytotoxic activity with IC50 0.074 µM.