Amir E. Wahba

Damietta University

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Mark T. Hamann

Medical University of South Carolina

Hoda M. Gebril

Rutgers, The State University of New Jersey

Safwat A. Ahmed

Suez Canal University

Amira A. El-Fallal

Damietta University

Tho Lai

Rutgers, The State University of New Jersey

Jiangnan Peng

Morgan State University

Eman S. Habib

Damietta University

Detlev Boison

Johnson University

Amany K. Ibrahim

Al-Azhar University

Denise E. Fedele

Johnson University

Cooperative Institutions

Seascape Consultants (United Kingdom)

263

Caterpillar (United States)

256

Pfizer (United Kingdom)

Chinese Academy of Sciences

University of Mississippi

Damietta University

Kyiv City Clinical Oncology Center

Chinese Academy of Medical Sciences & Peking Union Medical College

South China Agricultural University

University of Chinese Academy of Sciences

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New cytotoxic cyclic peroxide acids from Plakortis sp. marine sponge

ARKIVOC (2015)

Thomas R. Hoye Walied M. Alarif Salim S. Basaif Mohamed Abo-Elkarm Mark T. Hamann

Bioassay-guided fractionation of the extract of Jamaican marine sponge Plakortis sp.followed by preparative TLC and HPLC yielded several known methyl ester cyclic peroxides (1a, 2a, 3a, 4, 5), known plakortides (6,7), known bicyclic lactone (8) and new cyclic peroxide acids (1b, 2b, 3b).The chemical structures were elucidated by extensive interpretation of their spectroscopic data.These natural products showed remarkable in vitro cytotoxicity against several cancer cell lines.

Sponge

Peroxide

Natural product

Organic peroxide

10.3998/ark.5550190.p008.948

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Citations (13)

Scale up synthesis of ART207, a paclitaxel-based lipophilic prodrug for tumor selective delivery via pseudo-LDL nanoparticles

Planta Medica (2014)

Amir E. Wahba MK Gundluru JT Henri Sujatha Venkataraman JD McChesney

The ultimate goal of an anticancer regime is to eliminate tumor cells without harming healthy cells. However, currently used chemotherapeutic drugs are not selective and hence attack both healthy and tumor cells which results in very serious side effects. Targeted delivery of anticancer drugs to tumors utilizing nanoparticles has been the focus of the scientific community as well as pharmaceutical companies with the hope of selectively delivering the drug to the cancer cell and increasing the efficacy of the drug while reducing systemic toxicity. Arbor Therapeutics has developed a targeted delivery approach based on the synthesis of acid-labile lipophilic prodrugs of approved clinical anticancer drugs and their formulation into pseudo-LDL nanoparticles for selective tumor delivery via over expressed LDL receptors. A paclitaxel-based lipophilic prodrug, ART207, has been synthesized starting from methyl oleate ester. Challenges of the scale-up process and the separation of ART206 stereoisomers will be discussed in detail. ART207 has shown cytotoxicity to several paclitaxel sensitive cell lines including prostate, breast and ovarian.

Targeted drug delivery

10.1055/s-0034-1382733

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New Synthetic Methodologies for the Construction and Optimization of Natural Products

Amir E. Wahba

Source

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ChemInform Abstract: Reductive Amidation of Nitroarenes: A Practical Approach for the Amidation of Natural Products.

ChemInform (2009)

Amir E. Wahba Jiangnan Peng Mark T. Hamann

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

10.1002/chin.200941074

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TumorSelect® Technology Enhancing the Safety and Efficacy of Cancer Chemotherapy

Research Square (Research Square) (2021)

S J Bannister Amir E. Wahba Mahesh Kumar Gundluru Igor Nikoulin Douglas L. Rodenburg

Abstract Veiled Therapeutics has developed an anticancer technology, TumorSelect ® Technology, which combines proprietary anticancer prodrugs and nanotechnology, which takes advantage from current knowledge of human physiology. Tumors have a voracious appetite for cholesterol which facilitates tumor growth and fuels their proliferation. We have transformed this need into a stealth delivery system to disguise and deliver anticancer drugs with the assistance of both the human body and the tumor cell. Veiled’s designer prodrugs are assembled within pseudo-LDL nanoparticulates which carry them to tumor tissues where they are taken up, internalized and transformed into active drug and kill the cancer cells. This three-prong approach delivers the anticancer drug selectively to the tumors and thereby avoids or reduces the severe side effect toxicities associated with current chemotherapy. Reduction of side effect toxicity of cancer therapy by our technology will improve patient quality of life, patient retention in treatment regimes, more rapid patient recovery post treatment, and overall patient benefit.A. BackgroundThe costs of cancer, measured in terms of mortality, morbidity, direct costs of treatment, and costs of lost productivity are high.B. MethodsART-207 was synthesized; a pseudo-LDL lipid nanodispersion was formed; and mouse xenograft studies were performed. C. ResultsPreclinical toxicity, efficacy, and distribution data clearly show significant advantages of TumorSelect ® paclitaxel over conventional Cremophor ® formulations of paclitaxel. These advantages include:· Increased suppression of tumor growth and regrowth· Lower toxicity· Increased survival· Higher number of tumor free animals· Significantly lower concentrations of paclitaxel in non-target tissues· Significantly higher concentrations of paclitaxel in tumor tissueThus, data obtained demonstrated targeted drug delivery and support LDL-receptor dependent mechanism of selective cellular uptake by tumor tissue of TumorSelect ® formulated paclitaxel.D. ConclusionsNon-target tissue concentrations of paclitaxel are significantly lower in non-tumored and tumored mice injected with formulated TumorSelect ® paclitaxel compared with the mice injected with Cremophor ® EL/EtOH (ethanol) paclitaxel (<20%).Tumor concentrations of paclitaxel are significantly higher in tumors of mice injected with formulated TumorSelect ® paclitaxel compared with the mice injected with Cremophor ® EL/EtOH paclitaxel (194%).Plasma and heart concentrations of paclitaxel are significantly lower in tumored vs. non-tumored animals injected with formulated TumorSelect ® paclitaxel (<80%).Selective cellular uptake of TumorSelect ® paclitaxel by tumors actively expressing LDL-receptors has been demonstrated.Tumor suppression observed was sustained for 63 days after Q1Dx5 dosing with TumorSelect ® paclitaxel.TumorSelect ® technology represents a potential major improvement in the clinical treatment of cancer through enhanced efficacy due to tumor-facilitated targeted delivery and reduced patient toxicity with its associated deleterious side effects.

10.21203/rs.3.rs-701601/v1

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Citations (1)

Adenosine Kinase Expression Determines DNA Methylation in Cancer Cell Lines

ACS Pharmacology & Translational Science (2021)

Amir E. Wahba Denise E. Fedele Hoda M. Gebril Enmar Alharfoush Kiran S. Toti

DNA methylation has a major role in cancer, and its inhibitors are used therapeutically. DNA methylation depends on methyl group flux through the transmethylation pathway, which forms adenosine. We hypothesized that an adenosine kinase isoform with nuclear expression (ADK-L) determines global DNA methylation in cancer cells. We quantified ADK-L expression (Western Blot) and global DNA methylation as percent 5-methyldeoxycytidine (5mdC, LC-MS/MS) in three cancer lines (HeLa, HepG2, and U373). ADK-L expression and global DNA methylation correlated positively with the highest levels in HeLa cells compared to U373 and HepG2 cells. To determine whether ADK increases global DNA methylation and to validate its potential therapeutics, we treated HeLa cells with potent ADK inhibitors MRS4203 and MRS4380 (IC50 88 and 140 nM, respectively). Both nucleosides, but not a structurally related poor ADK inhibitor, significantly reduced global DNA methylation in HeLa cells in a concentration-dependent manner. Thus, ADK-L is a potential target for the therapeutic manipulation of DNA methylation levels in cancer.

HeLa

Adenosine kinase

10.1021/acsptsci.1c00008

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International Journal of Pharmaceutical Sciences and Research (2017)

Rania Abou El-Ezz Amany K. Ibrahim Eman S. Habib Amir E. Wahba Haidy Kamel

The marine environment is a rich source of both biological and chemical diversity.This diversity has been the source of unique chemical compounds with potential for drug development.In recent years, a significant number of novel metabolites with potent pharmacological properties have been discovered from the marine organisms.Specifically, the Red Sea is a natural source of these bioactive compounds.The Red Sea is a rich source of marine organisms that contain bioactive substances with intriguing and unique structural features.Examples of marine organisms commonly found in the Red Sea are sponges, soft corals, and algae.Secondary metabolites obtained from Red Sea marine organisms have been reported to show various biological activities such as: cytotoxic, antiproliferative, antiviral and anti-inflammatory activities.This review emphasizes the bioactivity of marine natural products specifically those isolated from the Red Sea.The present article highlights the latest progress in both chemistry and biological activities of metabolites isolated from Red Sea organisms till year 2014, also it provides a perspective on future areas of research interest.This review contains 435 structures and 138 references. INTRODUCTION:The marine environment is a rich source of both biological and chemical diversity.This diversity is immense and therefore is an extraordinary resource for the discovery and development of various novel drug leads.Because of the different physical and chemical conditions found in the marine environment, almost every class of marine organism affords a variety of molecules with unique structural features.Research into the biological as well as pharmacological properties of marine natural products has led to the discovery of many potently active agents considered worthy of clinical application.

10.13040/ijpsr.0975-8232.8(3).940-74

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Synthesis and application of LGB/St/Al2O3 biocomposite for sensitive detection and efficient removal of brilliant green dye from wastewater

Journal of environmental chemical engineering (2018)

E.A. Moawed Amir E. Wahba RabeiM. Gabr

Biocomposite

Brilliant green

10.1016/j.jece.2018.11.017

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Citations (15)

New One-Pot Methodologies for the Modification or Synthesis of Alkaloid Scaffolds

Marine Drugs (2010)

Amir E. Wahba Mark T. Hamann

There are several avenues by which promising bioactive natural products can be produced in sufficient quantities to enable lead optimization and medicinal chemistry studies. The total synthesis of natural products is an important, but sometimes difficult, approach and requires the development of innovative synthetic methodologies to simplify the synthesis of complex molecules. Various classes of natural product alkaloids are both common and widely distributed in plants, bacteria, fungi, insects and marine organisms. This mini-review will discuss the scope, mechanistic insights and enantioselectivity aspects of selected examples of recently developed one-pot methods that have been published in 2009 for the synthesis of substituted piperidines, quinolizidines, pyrrolidines, hexahydropyrrolizines, octahydroindolizines and g-lactams. In addition, progress on the synthesis of b-carboline (manzamine) alkaloids will also be discussed.

Natural product

Scope (computer science)

10.3390/md8082395

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Citations (22)

Regio-controlled Nitration of Manzamine A as Intermediates for Producing Manzamine Analogues with Better Docking Scores with GSK-3?

Planta Medica (2008)

Amir E. Wahba Jia Peng P. Sivaprakasam Srinivas Odde RJ Doerksen

The manzamines are a unique group of sponge derived alkaloids containing a complex polycyclic system with a β-carboline moiety. Manzamine A shows significant antimalarial activity with IC50 4.5 ng/mL and was identified as a new class of human Glycogen Synthase Kinase-3 (GSK-3β) inhibitors. The structure of this protein is known from X-ray and the protein plays many roles in signaling pathways and phosphorylation of glycogen synthase. Docking studies of manzamine A and 8-hydroxmanzamine A in the non-ATP binding site of GSK-3β show that the manzamines fit very nicely. The GOLD docking pose showed polar residues close to the benzene ring of the β-carboline moiety, which suggested that modification at the 5–8 positions would provide analogues, which would bind better to this pocket. Nitro products of manzamine A at the 6- & 8- positions were obtained by direct nitration of manzamine A while nitration at the 5- & 7- positions were achieved by using 8-hydroxymanzamine A as starting material.

Moiety

Docking (animal)

10.1055/s-2008-1075238

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