Designing, Synthesis and testing novel radiotheranostic molecules for positron emission tomography (PET) imaging and treatment of castration resistant prostate cancer.
Focused on the development of a new synthetic method targeting novel NRSG12D Inhibitors. Synthesizing the targeted library of fully substituted pyrimidine and benzene derivative required modifications in previously reported methods. A microwave synthetic method was developed for Suzuki coupling reactions (aryl halides and secondary aliphatic cyclic amines) and Buchwald-type reactions (aryl halides and aliphatic alcohol). Through the developed method, a strategic protecting groups were designed to be removed in one step. The developed microwave assisted method offers a quick transformation/coupling reactions and saves long time to develop up to 10 compounds a week after five step reactions.Design and synthesis of novel routes towards total synthesis of KB343 targeting its core structure via developing oxidative dearomatization (OD) reactions of guanidine derivatives containing anisole moiety. Therefore, OD reactions of different derivatives of urea, thiourea, guanidine, and carbamate have been investigated to define the best derivative with specific blocked groups which ultimately lead to good conversion/cyclization to/of desired spiro structure. Three different routes have been optimized to access the core structure within few steps.
Biological activity of most of the isolated chemical structures have been investigated against globally distributed diseases. Synthesized specific derivatives of thiazolidines by improving their chemical stability and studied their antiproliferative activity. Group of thiazolidines have induced apoptotic activity in esophageal tumors cell lines via inhibitions of ERK pathway. In addition to the thiazolidines, benzothiazole derivatives derived from OD reactions as a previously unreported synthetic method. However, benzothiazoles were undesired cyclized products from OD reactions, they have been tested for their neurological activity and their activity towards GABA regulated genes. Acetated benzothiazole derivative significantly decreased Gabreg2 gene expression and it was significantly decreased by 2.25-fold which referring to a possible potential activity of benzothiazole against epileptic seizures. Another benzothiazole derivative increase the expression of Scl7a11 gene that is ultimately regulate conversion of toxic lipid ROS into non-toxic species, thus it participates in a primary cellular mechanism of protection against ferroptosis. Therefore, identifying benzothiazoles effect on series of lipid mediators using LCMS/MS technique has been running.
Investigated a possible mechanism for cyclization of urea and thiourea derivatives via OD reactions through calculation of possible transition states involving in each cyclization using Gaussian software. Also, exploring theoretically the mechanism of F420-dependent glucose-6-phosphate dehydrogenase through calculating transition states and identifying whether it is a concerted or a stepwise reaction. The data shows that last step of hydrogen transfer reaction goes through a different amino acid and not the reported one based on complex geometry which makes the proposed amino acid (glutamic acid) residue far away from the nitrogen in F420. While a resonance structure in F420 pyrimidine happened to drive a negative charge on the oxygen of neighboring carbonyl which is further attacked by hydrogen from the neighboring histidine moiety.
New reaction development; synthetic routes for the synthesis of complex molecules
Synthesis radiolabeled molecules for PET imaging
Design new medicinal chemistry projects
Proficient with one- and two-dimensional Nuclear Magnetic Resonance (NMR) spectroscopy and data analysis using MestRec/MNova software
HPLC, LCMS, and GC
LCMS/MS for lipidomic and metabolomics identification techniques
Compound purification using a variety of chromatographic methods (flash, automated purification systems)
Computational techniques (Study reaction mechanism using Gaussian, Docking, QSAR)
In-vivo and in-vitro bioassays