Amany Mostafa Ahmed Osman

High physiological thermal triplex stability optimization of twisted intercalating nucleic acids (TINA)

The structure of the monomer (R)-1-O-[4-(1-pyrenylethynyl)phenylmethyl]glycerol () in twisted intercalating nucleic acids (TINA) was optimized for stabilizing interactions between the intercalator and surrounding nucleobases when used as a triplex forming oligonucleotide (TFO). Enhancement of pi-pi interactions with nucleobases of the TFO was achieved by increasing the aromatic surface using the (R)-1-O-[4-(1-pyrenylethynyl)naphthylmethyl]glycerol monomer (). Bulge insertion of in the middle of a Hoogsteen-type triplex increased the triplex thermal stability, DeltaT(m) = +2.0 degrees C compared with at pH 7.2. Syntheses and thermal denaturation studies of triplexes and duplexes are described for three novel TINA monomers. The influence of pi-pi interactions, link length and the positioning of the ether in the linker in the TINA derivatives are described.

Synthesis and Evaluation of Thalidomide and Phthalimide Esters as Antitumor Agents

A series of thalidomide and phthalimide ester analogs were efficiently synthesized from N‐chloromethylthalidomide, N‐chloromethylphthalimide, and N‐(2‐bromoethyl)phthalimide derivatives with various biologically important carboxylic acids. The synthesized compounds were purified and characterized by various chromatographic and spectroscopic techniques. The antitumor activity of all the synthesized compounds was screened against human liver and breast cancer cells, which showed that phthalimide ester 6a was the best cytotoxic compound against MCF7 cells, while all of the tested compounds showed a non‐cytotoxic effect against HepG2 cells. Compounds 5a, 6a, and 7a possess immunosuppressant effect, while compounds 5c, 5d, 6c, 6d, 7c, and 7d showed an immunostimmulatory effect. Meanwhile, estimation of the binding affinity for all the synthesized compounds toward the vascular endothelial growth factor receptor (VEGFR) showed that compounds 5a, 5b, and 7d were the most potent inhibitors.

Synthesis of A New Intercalating Nucleic Acid 6H-INDOLO[2,3-b] Quinoxaline Oligonucleotides to Improve Thermal Stability Of Hoogsteen-Type Triplexes

A new intercalating nucleic acid monomer X was obtained in high yield starting from alkylation of 4-iodophenol with (S)-(+)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethanol under Mitsunobu conditions followed by hydrolysis with 80% aqueous acetic acid to give a diol which was coupled under Sonogashira conditions with trimethylsilylacetylene (TMSA) to achieve the TMS protected (S)-4-(4-((trimethylsilyl)ethynyl)phenoxy)butane-1,2-diol. Tetrabutylammonium flouride was used to remove the silyl protecting group to obtain (S)-4-(4-ethynylphenoxy)butane-1,2-diol which was coupled under Sonogashira conditions with 2-(9-bromo-6H-indolo[2,3-b]quinoxalin-6-yl)-N,N-dimethylethanamine to achieve (S)-4-(4-((6-(2-(dimethylamino)ethyl)-6H-indolo[2,3-b]quinoxalin-9-yl)ethynyl)phenoxy)butane-1,2-diol. This compound was tritylated with 4,4′-dimethoxytrityl chloride followed by treatment with 2-cyanoethyltetraisopropylphosphordiamidite in the presence of N,N′-diisopropyl ammonium tetrazolide to afford the corresponding phosphoramidite. This phosphoramidite was used to insert the monomer X into an oligonucleotide which was used for thermal denaturation studies of a corresponding parallel triplex.

Synthesis, Biological Evaluation, Docking and QSAR Studies of SomeNovel Naphthalimide Dithiocarbamate Analogs as Antitumor and Anti-Inflammatory Agents

A series of novel naphthalimide dithiocarbamate 4a-f, 5a-f were efficiently synthesized via introduce dithiocarbamate and dithioate side chain onto the naphthalic anhydride core. The structures of the synthesized analogs were elucidated by spectroscopic methods, including IR,1H and 13C NMR, and (ESIHRMS) techniques. The anti-cancer activities of the generated naphthalimide derivatives 4c, 4d, 4e, 4f, and 5d were evaluated against 21 tumour cell lines; inculding 10 tumor subpanels using MTT assay. Analogue 4c offer antitumor activity with an IC50 of 10.54 μM against SKBR3 breast cancer cells. Compound 4d showed varying degrees of antitumor activities towards several tumour cell lines ranging from 21.1 to 71.7 μM. In addition to the antitumor activities; the synthesized compounds were evaluated for their In vitro anti-inflammatory activity. Compounds 4c and 4d revealed potent anti-inflammatory properties in comparison with the reference drug celecoxib. Molecular docking studies provided complementary theoretical support for experimental biological data.