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Staff Researches

khairia M. Youssef

N-substituted-piperidines as Novel Anti-alzheimer Agents: Synthesis,

Khairia Mohamed Ahmed Youssef

Iten M. Fawzy a, Hussein I. El-Subbagh

Future Journal of Pharmaceutical Sciences

2017

Design, synthesis and evaluation of new acetylcholinesterase inhibitors by combining carbamoylpiperidine analogs containing nipecotic acid scaffold were described. Then, a series of hybrids have been developed by introducing Free radical scavengers. Molecular modeling was performed and structure activity relationships are discussed. Among the series, most potent compounds showed effective AchE inhibitions, high selectivity over butyrylcholinesterase and high radical scavenging activities. On the basis of this work, the ability of analogs containing nipecotic acid scaffold to serve in the design of Nbenzyl- piperidine linked multipotent molecules for the treatment of Alzheimer Disease.

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Curcumin Analogs with anticipated anticancer activityIten M. Fawzy1, Khairia M. Youssef¬¬1, Nasser S. M. Ismail2, J. Gullbo3 and Khaled A. M. Abouzid¬2.1Pharmaceutical chemistry Dept. Faculty of Pharmaceutical Sciences & Pharmaceutical Industries, Future University, Cairo, 12311, Egypt.

Khairia Mohamed Ahmed Youssef

FUE Journal

2015

Six novel curcumin analogs were designed, synthesized with 3,5-dibenzylidenepiperidin-4-one core moiety and three of them were evaluated for their antitumor activities in 5 different cell lines; [ovarian cancer (A2780), renal adenocarcinoma (ACHN), prostate cancer (PC-3), colorectal cancer (Hct-116) and a leukemic monocyte lymphoma (U937-GTB)]. Also in silico molecular docking was performed on the six curcumin analogs to predict their binding affinity to tubulin enzyme and their ability to destabilize microtubules through interaction energy docking scores compared to that of podophyllotoxin. Three of newly synthesized compounds were tested in vitro for their effect on tubulin polymerization.

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Design and synthesis of potential Ribonucleotide reductase enzyme (RNR) inhibitors as antileukemic and/or antiviral 2'-Deoxymethylene Nucleosides

Khairia Mohamed Ahmed Youssef

Prof. Dr. Eric J. Lien

Future Journal of Pharmaceutical Sciences

2015

In order to improve the antitumor and/or antiviral activities of existing nucleoside analogs, eight new compounds (9a,b, 14a,b, 15a,b and 16a,b) were designed and synthesized. Halogen atom were incorporated at the 2-position of the purine base to render the amino group at the 6-position less susceptible to metabolism by adenosine deaminase. A methylene group was introduced at the 2'-position following the lead of nucleoside antibiotics angustmycin A and neplanocin A. The two key intermediates 9a and 9b were prepared from guanosine after protection of the 3' and 5' hydroxyl groups and oxidation of the 2' hydroxyl group to the corresponding carbonyl group using swern method. The conversion of the carbonyl group to the methylene function was carried out by applying wittig reaction conditions. The final compounds 14 a,b, 15 a,b, 16 a,b were prepared by means of nonaqueous diazotization of 9a and 9b. The prepared compounds were subjected to in vitro antileukemic and antiviral activity upon a new L1210 cell line that is doubly resistant to both hydroxyurea and deoxyadenosine which was grown and characterized. The new compounds showed potent antileukemic activity.

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2- A Comprehensive Introduction to Medicinal and Pharmaceutical Chemistry.

Khairia Mohamed Ahmed Youssef

Mohamed A. Al-Omar, Mohamed M. Hefnawy, Abdulrahman M. Al-Obaid, Hussein I. El-Subbagh

Al-Rushd bookstore for publishing and distributing, Riyadh, Saudi Arabia.

2005

This book presents basic and advanced principles underlying a comprehensive introduction that are prevalent in pharmaceutical chemistry. To illustrate important or complex concepts, the book provides up-to-date examples of drug synthetic reactions, molecules, receptors, and their biological benefits. A comprehensive introduction to medicinal chemistry is consists of nine chapters. The concept of physicochemical properties of drug has been covered in this textbook. Over the past 15 years, diverse disciplines have generated a growing interest in the pharmaceutical application of drug design. The goal of this book is to share the findings in this exciting area of research by providing a systematic summary of case studies of Structure Activity Relationship.

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Design, synthesis and molecular modeling study of certain VEGFR-2 inhibitors based on thienopyrimidne scaffold as cancer targeting agents.

Khairia Mohamed Ahmed Youssef

Amna Ghith, Khairia M. Youssef , Nasser S. M. Ismail, Khaled A. M. Abouzid

Bioorganic Chemistry, 83, 2019, 111-128

2018

Different seriesof novel thieno [2,3-d]pyrimidine derivative (9a-d,10a-f,l,m and15a-m) were designed, synthesized and evaluated for their ability to in vitro inhibit VEGFR-2 enzyme. Also, the cytotoxicity of the final compounds was tested against a panel of 60 different human cancer cell lines by NCI. The VEGFR-2 enzyme inhibitoryresultsrevealedthatcompounds10d,15dand15gareamongthemostactiveinhibitorswithIC50 valuesof2.5,5.48and2.27µMrespectively,whilecompound10aremarkablyshowedthehighestcellgrowth inhibitionwithmeangrowthinhibition(GI)percentof31.57%.Itexhibitedbroadspectrumanti-proliferative activityagainstseveralNCIcelllinesspecificallyonhumanbreastcancer(T7-47D)andrenalcancer(A498)cell lines of 85.5% and 77.65% inhibition respectively. To investigate the mechanistic aspects underlying the activity,furtherbiologicalstudieslikeflowcytometrycellcycletogetherwithcaspase-3colorimetricassayswere carried on compound 10a. Flow cytometric analysis on both MCV-7 and PC-3 cancer cells revealed that it inducedcell-cyclearrestintheG0-G1phaseandreinforcedapoptosisviaactivationofcaspase-3.Furthermore, molecular modeling studies have been carried out to gain further understanding of the binding mode in the activesiteofVEGFR-2enzymeandpredictpharmacokineticpropertiesofallthesynthesizedinhibitors.

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Medicinal Attributes of Thienopyrimidine Based Scaffold Targeting

Khairia Mohamed Ahmed Youssef

Amna Ghith1, Nasser S.M. Ismail 1, Khaled A.M. Abouzid2

Arch. Pharm. Chem. Life Sci.

2017

Thienopyrimidines (TP), comprising a thiophene ring fused with pyrimidine, are famous bioisosteres to purines, an essential part of the human metabolome. This scaffold has become an interesting structural element in the development of pharmaceutical compounds, due to their wide spectrum applications as cytotoxic agents against different types of human cancer cell lines, cGMP phosphodiesterase inhibitors, and anti-viral, anti-inflammatory, and anti-microbial agents. The structural similarity of this scaffold with adenine made it an excellent moiety to be used in the design of kinase inhibitors. This review focuses on the chemistry of thienopyrimidine derivatives, their potential activities against various kinases, and their structure–activity relationship studies.

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Synthesis of Curcumin Analogues as Potential Antioxidant, Cancer Chemopreventive

Khairia Mohamed Ahmed Youssef

Khairia M. Youssef, Magda A. El-Sherbeny, Faiza S. El-Shafie, Hassan A. Farag, Omar A. Al-Deeb, Sit Albanat A. Awadalla.

Arch. Pharm. Pharm. Med. Chem. 2004, 337, 42-54.

2004

Synthesis of Curcumin Analogues as Potential Antioxidant, Cancer Chemopreventive Agents.

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Synthesis of certain pyrazolo[1,2-a]indazole-1,3,9-trione derivatives of potential biological interest: part I.

Khairia Mohamed Ahmed Youssef

Mohga M. Badran, Mohamid A. Hamid Ismail, Khairia M. Youssef, Nadia Abdu and Maha Abdel-Hakeem

Alex. J. Pharm. Sci., 13 (1), 68-73 (1999).

1999

Synthesis of certain pyrazolo[1,2-a]indazole-1,3,9-trione derivatives of potential biological interest: part I.

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Synthesis and Phosphodiesterase inhibiting activity of some 6-subsituted-4,5-dihydro-pyridazin-3(2H)-ones.

Khairia Mohamed Ahmed Youssef

K.A.M. Abou-Zeid, K. M. Youssef, M.A. Shaaban, F.A. El-Telbany and S. H. Al- Zanfaly

Bull. Fac. Pharm.,33, 25-28 (1995).

1995

Synthesis and Phosphodiesterase inhibiting activity of some 6-subsituted-4,5-dihydro-pyridazin-3(2H)-ones.

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Attempts synthesis of spiro [3H-Indole-3,5-(4H) [1,3,4]oxadiazole].Effect of acetic anhydride on (2-oxo-3H-indol-3-ylidene) hydrazides.

Khairia Mohamed Ahmed Youssef

Adel A. El-Gendy, Refaat H. Omar and Khairia M. Youssef

International conference of pharmaceutical sciences and technology.

1995

Attempts synthesis of spiro [3H-Indole-3,5-(4H) [1,3,4]oxadiazole].Effect of acetic anhydride on (2-oxo-3H-indol-3-ylidene) hydrazides. ;

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Attempts synthesis of spiro [3H-Indole-3,5-(4H) [1,3,4]oxadiazole].Effect of acetic anhydride on (2-oxo-3H-indol-3-ylidene) hydrazides.

Khairia Mohamed Ahmed Youssef

Adel A. El-Gendy, Refaat H. Omar and Khairia M. Youssef

International conference of pharmaceutical sciences and technology. Alexandria March 22-25, (1995).

1995

Attempts synthesis of spiro [3H-Indole-3,5-(4H) [1,3,4]oxadiazole].Effect of acetic anhydride on (2-oxo-3H-indol-3-ylidene) hydrazides. ;

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Synthesis of some 4-substituted pyrimidinyl-6-aryl-1,2,5,6-tetrahydro-2-thioxopyrimidine derivatives as possible antimicrobial agents.

Khairia Mohamed Ahmed Youssef

K. M. Youssef and M. Badran

Egypt. J. Pharm. Sci.,33,No. 1-2, pp. 121-128 (1992).

1992

Synthesis of some 4-substituted pyrimidinyl-6-aryl-1,2,5,6-tetrahydro-2-thioxopyrimidine derivatives as possible antimicrobial agents.

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