Short Communication - Journal of Clinical Haematology (2020) Volume 1, Issue 3
Anticancer Activity of S-Glycosylated Quinazoline Derivatives
Ahmed I. Khodair1*, Mona A. Alsafi2
1Chemistry Department, Faculty of Science, Kafrelsheikh University, 33516 Kafrelsheikh, Egypt
2Chemistry Department, College of Science, Taibah University, 1343 Al-Madinah Al-Monawarah, Saudi Arabia
- *Corresponding Author:
- Ahmed I. Khodair
E-mail:khodair2020@yahoo.com
Received date: September 08, 2020; Accepted date: October 22, 2020
Citation: Khodair AI, Alsafi MA. Anticancer Activity of S-Glycosylated Quinazoline Derivatives. J Clin Haematol. 2020; 1(3):72-77.
Copyright: © 2020 Khodair AI, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Breast cancer is the most frequent malignancy in females. Due to its major impact on the population, this disease represents a critical public health problem that requires further research at the molecular level to define its prognosis and specific treatment. Basic research is required to accomplish this task and this involves cell lines as they can be widely used in many aspects of laboratory research and, particularly, as in vitro models in cancer research. MCF-7 is a commonly used breast cancer cell line, that has been promoted for more than 40 years by multiple research groups but its characteristics have never been gathered in a consistent review article. The current paper provides a broad description of the MCF- 7 cell line, including the molecular profile, proliferation, migration, invasion, spheroid formation, its involvement in angiogenesis and lymphangiogenesis, and its interaction with the mesenchymal stem cells [1].
Breast cancer is a commonly diagnosed cancer and a leading cause of cancer-related death in women worldwide [2]. It remains an area of active research both clinically and experimentally. Recent advances in metabolomics show that metabolic profiling can be useful for the identification of biomarkers in breast cancer. Metabolic profiles of human breast cancer show differences among breast cancer subtypes and offer a way to identify and develop strategies for precise prevention and treatment [3-5]. Obesity is a risk factor for breast cancer; its occurrence is positively associated with the risk of breast cancer [6,7]. Obesity is a modern disorder that has resulted, not just from changes in energy balance, but from changes in lifestyle that alter meal times and eating patterns [8,9]. These changes, as environmental factors, disrupt biological rhythms and contribute to metabolic dysfunction [10,11]. Laboratory studies have shown that the feeding timing modifies obesogenic in rodents. For example, mice fed with a high-fat diet (HFD) during the light phase (rest phase for nocturnal animals) gain more weight than mice fed during the dark phase (active phase for nocturnal animals) [12]. Mice fed with an HFD during both light and dark phases exhibit altered daily pattern of energy expenditure and gain body fat [13]. Time-restricted feeding (TRF) is an effective tool in obesity research in rodents. It reinforces the circadian rhythms of energy metabolism by temporal regulation of the feeding/fasting pattern to a fixed time during the dark phase of the day. Available studies have shown that TRF restores the diurnal rhythms of energy metabolism [11] and circadian gene expression [14], improves insulin sensitivity, and reduces body adiposity and inflammation in mice fed with an HFD [13-15].
According to the world health organization (WHO), cancer is an important health problem that claims the level of more than 7 million people worldwide on an annual basis [16,17]. Because of the limitation of surgery and radiotherapy in effecting a cure for cancer, chemotherapy has been increasingly important [16,17]. Therefore, identification of novel potent, selective, and less toxic anticancer agents remains one of the most pressing health problems. In the vast cancer chemotherapeutic space, glycosides have played a very important role as established cancer chemotherapeutic agents, either in their nature, semi-synthetically, or synthetically forms [18-73]. As cited above, among the natural glycosides based antitumor the antibiotic doxorubicin, anthracycline O-glycoside, ranks among the most effective anticancer drug for acute myelocytic leukemia [20-22]. Furthermore, many sugar modified nucleoside analogues are clinically useful chemotherapeutics [18]. For example, capecitabine [29], N-nucleoside and C-nucleoside, are applied in the treatment of metastatic breast cancer and hairy cell leukaemia, respectively. Recently, several S-glycosides, a new non-classical class of nucleosides, have been proved to be potential anticancer agents against many cell Lines [32-37]. Khodair et al. described the synthesis of a series of heterocyclic S-glycosides, thiohydantoins [47-59], rhodanines [60], thioquinazolines [61,62], thiopyridines [63-65], and thiopyrimidine [66] S-glycosides and revealed their potential antitumor activities.
Our research interest focused on the design and synthesis of new small heterocyclic nucleosides targeting cancer especially MCF-7 and HepG2 cell lines. The elaboration of quinazoline derivatives linked with glycopyranose sugars (Figure 1) to form the target nucleosides was our task [61,64]. The in vitro cytotoxic activity against MCF- 7 and HepG2 cell lines showed effective anti-proliferative activity of the analyzed derivatives with lower IC50 values especially 2a with IC50 =2.09 and 2.08 μM against MCF-7 and HepG2, respectively, and their treatments were safe against the normal cell line Gingival mesenchymal stem cells (GMSC). Moreover, RT-PCR reaction investigated the apoptotic pathway for the compound 2a, which activated the P53 genes and its related genes. So, further work is recommended for developing it as a chemotherapeutic drug. We found that anticancer activity of the promising derivatives 1a,b and 2a,b was tested against breast (MCF- 7), liver (HepG2) cell lines by measuring the percentage of cell survival against their serial dilutions (0.01, 0.1, 1, 10, and 100 μM) [61]. Moreover, they were screened against the GMSC as normal cell line to test their safety [66]. We conclude the incorporation of sugar portion to the nucleus, enhanced the cytotoxic activity against the MCF-7 and HepG2 cell lines by having lower IC50 values, as shown in Table 1. Although both compounds 2a and 2b have near IC50 values (2.09 and 2.04 μM, respectively) against HepG2 cells, 2a was considered as the lead compound in our study according to the molecular docking results. It has a higher binding affinity towards the EGFR tyrosine kinase receptor because it forms a larger number of hydrogen bonds with the key amino acid residue Met 769 compared to other derivatives, so it was selected for further testing as the molecular mode of action. An attempt to study the structure-activity relationship using the molecular docking tool for elucidation the binding interactions of the nucleosides which might justify their higher potency [66]. Glycosides of structurally similar heterocyclic systems have been reported before [47-73].

| IC50 (μM) |
---|
| MCF-7 | HepG2 | GMSC |
5-FU | 4.23 | 4.43 | > 50 |
1a | 5.93 | 3.79 | > 50 |
1b | 2.42 | 1.17 | ND |
2a | 2.09 | 2.08 | > 50 |
2b | 2.04 | 2.09 | > 50 |
Table 1: Summarized IC50 for the activity of the analyzed compounds against the MCF-7 and HepG2 cell lines.
The nucleoside bases 3-substituted 2-thioxo-2,3-dihydro- 1H-quinazolin-4-ones and 3-substituted 2-thioxo-2,3- dihydro-1H-benzo[g]quinazolin-4-ones can be utilized as starting materials for the synthesis of other carbohydrate derivatives as deoxy, amino and azido nucleosides.
References
- Com?a ?, Cimpean AM, Raica M. The story of MCF-7
breast cancer cell line: 40 years of experience in research.
Anticancer Research. 2015 Jun 1;35(6):3147-54.
- Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre
LA, Jemal A. Global cancer statistics 2018: GLOBOCAN
estimates of incidence and mortality worldwide for
36 cancers in 185 countries. CA: A Cancer Journal for
Clinicians. 2018 Nov;68(6):394-424.
- Giskeødegård GF, Grinde MT, Sitter B, Axelson DE,
Lundgren S, Fjøsne HE, et al. Multivariate modeling and
prediction of breast cancer prognostic factors using MR
metabolomics. Journal of Proteome Research. 2010 Feb
5;9(2):972-9.
- Sitter B, Bathen TF, Singstad TE, Fjøsne HE, Lundgren
S, Halgunset J, et al. Quantification of metabolites in
breast cancer patients with different clinical prognosis
using HR MAS MR spectroscopy. NMR in Biomedicine:
An International Journal Devoted to the Development
and Application of Magnetic Resonance In vivo. 2010
May;23(4):424-31.
- Tang X, Lin CC, Spasojevic I, Iversen ES, Chi JT, Marks
JR. A joint analysis of metabolomics and genetics of breast
cancer. Breast Cancer Research. 2014 Aug;16(4):1-5.
- Picon-Ruiz M, Morata-Tarifa C, Valle-Goffin JJ,
Friedman ER, Slingerland JM. Obesity and adverse
breast cancer risk and outcome: Mechanistic insights
and strategies for intervention. CA: A Cancer Journal for
Clinicians. 2017 Sep;67(5):378-97.
- Rohan TE, Heo M, Choi L, Datta M, Freudenheim
JL, Kamensky V, et al. Body fat and breast cancer risk in
postmenopausal women: a longitudinal study. Journal of
Cancer Epidemiology. 2013 Jan 1;2013.
- Bae SA, Fang MZ, Rustgi V, Zarbl H, Androulakis
IP. At the interface of lifestyle, behavior and circadian
rhythms: Metabolic implications. Frontiers in Nutrition.
2019;6:132.
- Maury E, Brichard SM. Adipokine dysregulation,
adipose tissue inflammation and metabolic syndrome.
Molecular and Cellular Endocrinology. 2010 Jan
15;314(1):1-16.
- Branecky KL, Niswender KD, Pendergast JS.
Disruption of daily rhythms by high-fat diet is reversible.
PlOS One. 2015 Sep 14;10(9):e0137970.
- Zarrinpar A, Chaix A, Panda S. Daily eating patterns
and their impact on health and disease. Trends in
Endocrinology & Metabolism. 2016 Feb 1;27(2):69-83.
- Arble DM, Bass J, Laposky AD, Vitaterna MH, Turek
FW. Circadian timing of food intake contributes to weight
gain. Obesity. 2009 Nov;17(11):2100-2.
- Sundaram S, Yan L. Time-restricted feeding reduces
adiposity in mice fed a high-fat diet. Nutrition Research.
2016 Jun 1;36(6):603-11.
- Hatori M, Vollmers C, Zarrinpar A, DiTacchio L,
Bushong EA, Gill S, et al. Time-restricted feeding without
reducing caloric intake prevents metabolic diseases
in mice fed a high-fat diet. Cell Metabolism. 2012 Jun
6;15(6):848-60.
- Chaix A, Lin T, Le HD, Chang MW, Panda S. Timerestricted
feeding prevents obesity and metabolic syndrome
in mice lacking a circadian clock. Cell metabolism. 2019
Feb 5;29(2):303-19.
- Gupta SP. Quantitative structure-activity relationship
studies on anticancer drugs. Chemical Reviews. 1994
Sep;94(6):1507-51.
- Keri G, Toth I. In “molecular path mechanisms and
new trends in drug research”, London, New York, Taylor
and Francis 1st edition. 227 (2003).
- Kren V, Martínková L. Glycosides in medicine:“The
role of glycosidic residue in biological activity”. Current
medicinal chemistry. 2001 Sep 1;8(11):1303-28.
- Buchanan JG, Edgar AR, Hutchison RJ, Stobie
A, Wightman RH. A new synthesis of formycin via
nitropyrazole derivatives. Journal of the Chemical Society,
Chemical Communications. 1980(5):237-8.
- Monneret C. Recent developments in the field of
antitumour anthracyclines. European Journal of Medicinal
Chemistry. 2001 Jun 1;36(6):483-93.
- Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni
L. Anthracyclines: molecular advances and pharmacologic
developments in antitumor activity and cardiotoxicity.
Pharmacological Reviews. 2004 Jun 1;56(2):185-229.
- Krohn K E. Topics in current chemistry. Anthracycline
Chemistry and Biology 282 (2008).
- Grdadolnik SG, Pristovšek P, Mierke DF. Vancomycin: conformational consequences of the sugar substituent.Journal of Medicinal Chemistry. 1998 Jun 4;41(12):2090-9.
- Zhang H, Qian DZ, Tan YS, Lee K, Gao P, Ren YR,
et al. Digoxin and other cardiac glycosides inhibit HIF-
1α synthesis and block tumor growth. Proceedings of the
National Academy of Sciences. 2008 Dec 16;105(50):19579-
86.
- Peterson LB, Blagg BS. Click chemistry to probe
Hsp90: synthesis and evaluation of a series of triazolecontaining
novobiocin analogues. Bioorganic & Medicinal
Chemistry Letters. 2010 Jul 1;20(13):3957-60.
- Moyer JD, Oliver JT, Handschumacher RE. Salvage
of circulating pyrimidine nucleosides in the rat. Cancer
Research. 1981 Aug 1;41(8):3010-7.
- Cadman E, Benz C. Uridine and cytidine metabolism
following inhibition of de novo pyrimidine synthesis by
pyrazofurin. Biochimica et Biophysica Acta (BBA)-Nucleic
Acids and Protein Synthesis. 1980 Oct 17;609(3):372-82.
- Saran A. Correlation between the conformation
of nucleoside antibiotics and their biological activity.
International Journal of Quantum Chemistry. 1989
Jan;35(1):193-203.
- Tiwari KN, Shortnacy-Fowler AT, Parker WB, Waud
WR, Secrist III JA. Synthesis and anticancer evaluation of
4′-C-methyl-2′-fluoro arabino nucleosides. Nucleosides,
Nucleotides and Nucleic Acids. 2009 Aug 11;28(5-7):657-
77.
- Pomeisl K, Votruba I, Holý A, Pohl R. Syntheses of
pyrimidine acyclic nucleoside phosphonates as potent
inhibitors of thymidine phosphorylase (PD-ECGF) from
SD-lymphoma. Nucleosides, Nucleotides and Nucleic
Acids. 2007 Nov 26;26(8-9):1025-8.
- Elgemeie GH, El-Enany MM, Ismail MM, Ahmed EK.
Nucleic Acid Components and Their Analogues: A Novel
and Efficient Method for the Synthesis of a New Class of
Bipyridyl and Biheterocyclic-nitro Gen Thioglycosides
from Pyridine-2 (1 H)-thiones. Nucleosides, Nucleotides
and Nucleic Acids. 2002 Nov 1;21(6-7):477-93.
- Rashad AE, Mahmoud AE, Ali MM. Synthesis
and anticancer effects of some novel pyrazolo [3, 4-d]
pyrimidine derivatives by generating reactive oxygen
species in human breast adenocarcinoma cells. European
Journal of Medicinal Chemistry. 2011 Apr 1;46(4):1019-
26.
- Saad HA, Moustafa AH. Synthesis and anticancer
activity of some new S-glycosyl and S-alkyl 1, 2, 4-triazinone
derivatives. Molecules. 2011 Jul;16(7):5682-700.
- Al-Mutairi MS, Al-Abdullah ES, Haiba ME, Khedr
MA, Zaghary WA. Synthesis, Molecular Docking and
Preliminary in-Vitro Cytotoxic Evaluation of Some
Substituted Tetrahydro-naphthalene (2’, 3’, 4’, 6’-Tetra-
O-Acetyl-β-D-Gluco/-Galactopyranosyl) Derivatives.
Molecules. 2012 Apr;17(4):4717-32.
- Scala S, Akhmed N, Rao US, Paull K, Lan LB, Dickstein
B, et al. P-glycoprotein substrates and antagonists cluster
into two distinct groups. Molecular Pharmacology. 1997
Jun 1;51(6):1024-33.
- Abu-Zaied MA, Nawwar GA, Swellem RH, El-Sayed
SH. Synthesis and screening of new 5-substituted-1, 3,
4-oxadiazole-2-thioglycosides as potent anticancer agents.
Pharmacol Pharmacy 3, 254 (2012).
- Ishiwata A, Munemura Y, Ito Y. Synergistic solvent
effect in 1, 2-cis-glycoside formation. Tetrahedron. 2008
Jan 1;64(1):92-102.
- Larsen JS, Zahran MA, Pedersen EB, Nielsen C.
Synthesis of triazenopyrazole derivativesas potential
inhibitors of HIV-1. Monatshefte für Chemie/Chemical
Monthly. 1999 Sep 1;130(9):1167-73.
- Storer R, Ashton CJ, Baxter AD, Hann MM, Marr
CL, Mason AM, et al. The synthesis and antiviral
activity of 4-fluoro-1-β-D-ribofuranosyl-1H-pyrazole-3-
carboxamide. Nucleosides, Nucleotides & Nucleic Acids.
1999 Feb 1;18(2):203-16.
- Manfredini S, Baraldi PG, Bazzanini R, Durini E,
Vertuani S, Pani A, et al. Pyrazole Related Nucleosides
5.1 Synthesis and Biological Activity of 2′-Deoxy-2′,
3′-dideoxy-and Acyclo-analogues of 4-Iodo-1-β-Dribofuranosyl-
3-carboxymethyl Pyrazole (IPCAR).
Nucleosides, Nucleotides & Nucleic Acids. 2000 Apr
1;19(4):705-22.
- Hafez HN, El-Gazzar AR, Nawwar GA. Synthesis,
biological and medicinal significance of S-glycosidothieno
[2, 3-d]-pyrimidines as new anti-inflammatory
and analgesic agents. European Journal of Medicinal
Chemistry. 2010 Apr 1;45(4):1485-93.
- Schmidt RR. New Methods for the Synthesis of
Glycosides and Oligosaccharides—Are There Alternatives
to the Koenigs-Knorr Method?[New Synthetic Methods
(56). Angewandte Chemie International Edition in English.
1986 Mar;25(3):212-35.
- Elgemeie GH, Zaghary WA, Amin KM, Nasr TM.
First synthesis of thiophene thioglycosides. Journal of
Carbohydrate Chemistry. 2009 Apr 7;28(3):161-78.
- Cristescu C, Czobor F. As-Triazine Derivatives
with Potential Therapeutic Action. XXVI. 1 Synthesis of 5-Substituted-6-Azauracil Acyclonucleosides. Nucleosides
& Nucleotides. 1998 Aug 1;17(8):1319-24.
- Abu-Zaied MA, El-Telbani EM, Elgemeie GH, Nawwar
GA. Synthesis and in vitro anti-tumor activity of new
oxadiazole thioglycosides. European Journal of Medicinal
Chemistry. 2011 Jan 1;46(1):229-35.
- Khodair AI, Gesson JP. A new approach for the
N-and S-galactosylation of 5-arylidene-2-thioxo-4-
thiazolidinones. Carbohydrate Research. 2011 Dec
27;346(18):2831-7.
- El-Barbary AA, Khodair AI, Pedersen EB, Nielsen
C. S-Glucosylated hydantoins as new antiviral agents.
Journal of Medicinal Chemistry. 1994 Jan;37(1):73-7.
- Khodair AI, El-Subbagh HI, El-Emam AA. Synthesis
of certain 5-substituted 2-thiohydantoin derivatives as
potential cytotoxic and antiviral agents. Bollettino Chimico
Farmaceutico. 1997 Sep;136(8):561-567.
- Al-Obaid AM, El-Subbagh HI, Khodair A, Elmazar
MM. 5-substituted-2-thiohydantoin analogs as a novel
class of antitumor agents. Anti-Cancer Drugs. 1996 Nov
1;7(8):873-80.
- Khodair AI. Glycosylation of 2-thiohydantoin
derivatives. Synthesis of some novel S-alkylated and
S-glucosylated hydantoins. Carbohydrate Research. 2001
Apr 23;331(4):445-53.
- Khodair AI. Synthesis of 2-thiohydantoins and their
S-glucosylated derivatives as potential antiviral and
antitumor agents. Nucleosides, Nucleotides and Nucleic
Acids. 2001 Sep 30;20(9):1735-50.
- Khodair AI, Ibrahimb ES. Synthesis of Hydantoin
Nucleosides with Naphthylmethylene Substituents in the
5-Position. Nucleosides, Nucleotides & Nucleic Acids.
1996 Nov 1;15(11-12):1927-43.
- Khodair AI. A Convenient Synthesis of Glycosylated
Hydantoins as Potential Antiviral Agents. Phosphorus,
Sulfur, and Silicon and the Related Elements. 1997 Mar
1;122(1):9-26.
- Khodair AI. Synthesis of arylidenehydrazonoand
glycopyranosylhydrazino-sulfonylbenzylidene-2,
4-imidazolidinediones as potential antiviral and
antitumoral agents. Carbohydrate Research. 1998
Feb;306(4):567-573.
- Khodair AI, Gesson JP. Sulfur Glycosylation Reactions
Involving 3-Allyl-2-thiohydantoin Nucleoside Bases as
Potential Antiviral and Antitumor Agents. Phosphorus,
Sulfur, and Silicon and the Related Elements. 1998 Nov
1;142(1):167-90.
- Khodair AI, El-Barbary AA, Abbas YA, Imam DR.
Synthesis, reactions and conformational analysis of
5-arylidene-2-thiohydantoins as potential antiviral agents.
Phosphorus, Sulfur, and Silicon and the Related Elements.
2001 Mar 1;170(1):261-78.
- Al-Masoudi IA, Khodair AI, Al-Soud YA, Al-Masoudi
NA. Synthesis of N-substituted 1-amino-2, 3-dihydro-1
H-imidazole-2-thione-N-nucleosides and S-glycosylated
derivatives. Nucleosides, Nucleotides and Nucleic Acids.
2003 Jun 1;22(3):299-307.
- Al-Masoudi NA, Al-Soud YA, Khodair AI. Some
2′-Modified 4′-Thionucleosides via Sulfur Participation
and Synthesis of Thio-Azt from 4′-Thiofuranoid 1,
2-Glycal. Phosphorus, Sulfur, and Silicon and the Related
Elements. 2003 Jun 1;178(6):1199-209.
- Khodair AI, El Sayed H, Al-Masoudi NA. Thiohydantoin
nucleosides. Synthesis approaches. Monatshefte für
Chemie/Chemical Monthly. 2004 Sep 1;135(9):1061-79.
- Khodair AI, Awad MK, Gesson JP, Elshaier YA.
New N-ribosides and N-mannosides of rhodanine
derivatives with anticancer activity on leukemia cell line:
Design, synthesis, DFT and molecular modelling studies.
Carbohydrate Research. 2020 Jan 1;487:107894.
- Khodair AI, Elsafi MA, Al-Issa SA. Simple and Efficient
Synthesis of Novel 3-Substituted 2-Thioxo-2, 3-dihydro-
1H-benzo [g] quinazolin-4-ones and Their Reactions with
Alkyl Halides and α-Glycopyranosyl Bromides. Journal of
Heterocyclic Chemistry. 2019 Sep;56(9):2358-68.
- Khodair AI, Alsafi MA, Nafie MS. Synthesis,
molecular modeling and anti-cancer evaluation of a series
of quinazoline derivatives. Carbohydrate Research. 2019
Dec 1;486:107832.
- Khodair AI, Al-Masoudi NA, Gesson JP. A new
approach to the synthesis of benzothiazole, benzoxazole,
and pyridine nucleosides as potential antitumor agents.
Nucleosides, Nucleotides and Nucleic Acids. 2003 Nov
1;22(11):2061-76.
- Khodair AI, Attia AM, Gendy EA, Elshaier YA, El-Magd
MA. Discovery of New S-Glycosides and N-Glycosides
of Pyridine-biphenyl System with Antiviral Activity
and Induction of Apoptosis in MCF 7 Cells. Journal of
Heterocyclic Chemistry. 2019 Jun;56(6):1733-47.
- Attia AM, Khodair AI, Gendy EA, El-Magd MA,
Elshaier YA. New 2-oxopyridine/2-thiopyridine derivatives
tethered to a benzotriazole with cytotoxicity on MCF7 cell
lines and with antiviral activities. Letters in Drug Design &
Discovery. 2020 Feb 1;17(2):124-37.
- Khodair AI, Ibrahim EE, Ashry EE. Glycosylation
of 2-thiouracil derivatives. A synthetic approach to
3-glycosyl-2, 4-dioxypyrimidines. Nucleosides &
Nucleotides. 1997 Apr 1;16(4):433-44.
- Khodair AI. A convenient synthesis of 2-Arylidene-
5H-thiazolo [2, 3-b] quinazo-line-3, 5 [2H]-diones and
their benzoquinazoline derivatives. Journal of Heterocyclic
Chemistry. 2002 Nov;39(6):1153-60.
- Khodair AI, Pedersen EB, Nielsen C. Synthesis of
Uridine with Methylene-2-thiohydantoin as 5-Substituent.
Liebigs Annalen der Chemie. 1994 Jun 13;1994(6):619-21.
- El-Barbary AA, Khodair AI, Pedersen EB, Nielsen
C. Synthesis and evaluation of antiviral activity of
2′-deoxyuridines with 5-methylene-2-thiohydantoin
substituents in the 5-position. Monatshefte für Chemie/
Chemical Monthly. 1994 May 1;125(5):593-8.
- El-Barbary AA, Khodair AI, Pedersen EB, Nielsen
C. Synthesis of 3′-Amino and 5′-Amino Hydantoin
2′-Deoxynucleosides. Nucleosides, Nucleotides & Nucleic
Acids. 1994 Mar 1;13(1-3):707-17.
- El-Barbary AA, Khodair AI, Pedersen EB. Synthesis
and antiviral evaluation of hydantoin analogues of AZT.
Archiv Der Pharmazie. 1994;327(10):653-5.
- El-Barbary AA, Khodair AI, Pedersen EB, Nielsen
C. Convergent synthesis of 2′, 3′-dideoxy-3′-mercapto
nucleosides—Potential anti-HIV agents. Monatshefte für
Chemie/Chemical Monthly. 1994 Aug;125(8):1017-25.
- Abdel-Bary HM, El-Barbary AA, Khodair AI, Megied
AE, Pedersen EB, Nielsen C. Synthesis of hydantoin
analogues of 3’-fluoro-3’-deoxythymidine (FLT). Bulletin
de la Société Chimique de France. 1995;2(132):149-55.