RSC Advances Blog

We are very pleased to introduce Tarek Aboul-Fadl, corresponding authors of the paper ‘Inversion kinetics of some E/Z 3-(benzylidene)-2-oxo-indoline derivatives and their in silico CDK2 docking studies‘. His article has been very well received and handpicked by our reviewers and handling editors as one of our HOT articles. Tarek told us more about the work that went into this article and what he hopes to achieve in the future. You can find out more about the author and his article below and find more HOT articles in our online collection.

Meet the author

Dr Tarek Aboul-Fadl is a Prof. of Medicinal Chemistry at Faculty of Pharmacy, Assiut University/Egypt. Dr Aboul-Fadl received his Ph.D. in Pharmaceutical Medicinal Chemistry from Assiut University (1994) under the channel system and joint supervision scheme between Assiut University and Josai University/Japan. Dr Aboul-Fadl performed his postdoctoral training as a postdoctoral research fellow and Scientist at Institute of Pharmaceutical Chemistry, University of Vienna, Austria (1997- 1998), Institute of Pharmacy and Food Chemistry, Friedrich-Alexander-Universität (FAU), Erlangen-Nürnberg, Germany (1999 and 2013) and Department of Medicinal Chemistry, University of Utah, USA (2001-2002 and 2004-2005). Dr Aboul-Fadl joined Department of Medicinal Chemistry as an assistant Prof. in 1994, then promoted to associate Prof. in 1999 and to Professor in 2004. Dr Aboul-Fadl is a member of Egyptian Syndicate of Pharmacists since 1984, Egyptian Society of Pharmacists since 1994, American Chemical Society since 2002, The Stop TB Partnership Working Group on New TB Drugs (WGND) since Feb. 2010 and Member of Drug Research Council of Egyptian Academy of Scientific Research and Technology since June 2018. He is the author or co-author of more than 130 papers in international peer-reviewed journals and conferences and he has 4 patents Furthermore, he is a reviewer and a member of editorial board of several international journals. Dr Aboul-Fadl’s research interests are currently focused on computer aided drug design, design and development of cell cycle inhibitors as a potential anticancer agents, design and development of antituburcular drugs and Prodrugs and chemical delivery systems. ( Web: https://cutt.ly/nxONkAT).

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
Atoms of a particular molecule can arrange distinctly in the space giving to what is called isomers. The later do not necessarily share similar chemical or physical properties. Moreover, they could exert different biological activity and even toxicity, the tragedy of the thalidomide drug is still in mind.

How big an impact could your results potentially have?
E/Z-Isomerization of some drugs such as Sunitinib “ an anticancer drug” and its analogs as our molecules can affect the bioavailability and the pharmacological activities. Accordingly the possibility of inversion of these isomers to each other worthy to be study for good shelf live, maximum biological activities and drug safety.

Could you explain the motivation behind this study?
Sunitinib as an anticancer drug is bound to its receptor in the form of Z-diastereomer, even though they were the E-diastereomer in solution. The E form must be isomerized to the Z form before binding as the E-diastereomer is inactive. This was the motive to study the rate of isomerization in a polar solvent as DMSO. Furthermore, generation of a good multiple regression equation for prediction of stability of the diastereomers based on Quantum mechanics parameters.

In your opinion, what are the key design considerations for your study?
Development of inexpensive new anti-cancer agents with good potency and offer both selectivity and lower toxicity.

Which part of the work towards this paper proved to be most challenging?
The most challenging part was the generation of the predictive equation from the Quantum mechanics parameters and the rate of isomerization.

What aspect of your work are you most excited about at the moment?
Agreement of the laboratory results with those obtained by applying the generated equation. This will lead to confident prediction for the isomerisation rates of similar molecules and possible wide application in the pharmaceutical field.

What is the next step? What work is planned?
In vitro study of the antiproliferative activity and CDK2 inhibitory activity of the synthesized compounds. Investigations of isomerization in non-polar solvents and buffer induced isomerization particularly physiological and simulated gastric fluids buffers in addition to photoisomerization of these compounds and similar analogues.

Inversion kinetics of some E/Z 3-(benzylidene)-2-oxo-indoline derivatives and their in silico CDK2 docking studies
Hany S. Mansour, Hend A. A. Abd El-wahab, Ahmed M. Ali and Tarek Aboul-Fadl
RSC Adv., 2021,11, 7839-7850
DOI: 10.1039/D0RA10672K, Paper

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We are very pleased to introduce Ruel McKenzie, corresponding authors of the paper ‘Breaking the bottleneck: stilbene as a model compound for optimizing 6π e⁻ photocyclization efficiency‘. His article has been very well received and handpicked by our reviewers and handling editors as one of our HOT articles. Ruel told us more about the work that went into this article and what he hopes to achieve in the future. You can find out more about the author and his article below and find more HOT articles in our online collection.

Meet the author

Dr. Ruel McKenzie was born and raised in Kingston, Jamaica. He is an assistant professor in the School of Polymer Science & Polymer Engineering at The University of Akron. Prior to his current role, Dr. McKenzie was an NRC Postdoctoral Fellow at the Air Force Research Laboratory at Wright-Patterson Air Force Base and a postdoctoral researcher at the Foundation for Research and Technology-Hellas in the Institute of Electronic Structure and Laser. His degrees are in chemical engineering and he is a graduate of the NYU Tandon School of Engineering (B.Sc. and Ph.D.) and Columbia University (M. Sc.). Dr. McKenzie’s research activities are primarily in the field of chemical physics/physical chemistry of soft matter. His research is focused on making advances in the areas of soft matter dynamics, enabling complex structures and multifunctional materials.

Could you briefly explain the focus of your article to the non-specialist (in one or two sentences only) and why it is of current interest?
Stilbene was used as a model compound to mechanistically understand and overcome some factors that have limited 6π e⁻ photocyclization reactions to dilute conditions – which essentially limited throughput. This is of interest because the synthesis of polycyclic aromatic compounds is typically conducted through such photochemical routes.

How big an impact could your results potentially have?
Polycyclic aromatic compounds have an array of emergent properties of interest to the materials science community. The results from this work will contribute to efforts to increase the production scale of polycyclic aromatic compounds that use similar photochemical routes. We demonstrated the utility of an alternative oxidizing agent to the convention which increased the throughput by over 10-fold and could be extended to high concentrations without the evolution of undesired products. We anticipate further work in screening other potential oxidizing agents that may be used for enhanced throughput. This work also highlighted the relevance of stereoconformation on the reaction dynamics and the impact of light source on the equilibrium conformation, especially as concentration increased.

Could you explain the motivation behind this study?
This study is part of a larger effort to understand and control the formation of complex architectures of polycyclic aromatic compounds and enabling synthesis of such compounds at high throughput using photochemical routes. The transformation of stilbene to phenanthrene represented the most basic molecular geometry that could be studied, and it afforded us the opportunity to monitor the photocyclization reaction in a straightforward manner.

In your opinion, what are the key design considerations for your study?
The key design considerations from this study were the impact of conformer and oxidizing agents on the reaction dynamics.

Which part of the work towards this paper proved to be most challenging?
Samples needed to be prepared in a dark room to maintain the integrity of the pure isomers and post-reaction removal of one of the oxidizing agents at high concentrations was a laborious process.

What aspect of your work are you most excited about at the moment?
We are currently excited about the revelation on the impact of the light source on the equilibrium stereoconformation, which is a design aspect of the reaction that appears to have been largely overlooked. The light source will drive the photoactive molecule to an equilibrium stereoconformation irrespective of the starting conformation. Understanding this relationship between physical aspects of the light source (such as wavelength and intensity) and equilibrium stereoconformation (or conformation pathway) will help to elucidate how complex structures are formed (or can be manipulated) during photochemical synthesis of polycyclic aromatic compounds.

What is the next step? What work is planned?
We are extending our current understanding of the mechanism of phenanthrene formation to study photocyclization in larger polycyclic aromatic molecules towards elucidating the mechanisms of forming complex geometries.

Breaking the bottleneck: stilbene as a model compound for optimizing 6π e⁻ photocyclization efficiency
Joshua Seylar, Dmytro Stasiouk, Davide L. Simone, Vikas Varshney, James E. Heckler and Ruel McKenzie
RSC Adv., 2021,11, 6504-6508
DOI: 10.1039/D0RA10619D, Paper

Submit to RSC Advances today! Check out our author guidelines for information on our article types or find out more about the advantages of publishing in a Royal Society of Chemistry journal.

Keep up to date with our latest HOT articles, Reviews, Collections & more by following us on Twitter. You can also keep informed by signing up to our E-Alerts.