Synthesis, in silico studies, and in vitro biological evaluation of newly-designed 5-amino-1H-tetrazole-linked 5-fluorouracil analog as a potential antigastric-cancer agent.

5-Fluorouracil (5FU) is a chemotherapy drug used to treat various cancers, such as colorectal, prostate, skin, pancreas, and stomach, as an ointment or solution. However, its consumption has several side effects. Therefore, a new derivative of fluorouracil containing 5-Amino-1H-tetrazole was designed and synthesized through multi-step synthesis to reduce urea excretion and toxicity. The effectiveness of the synthesized drug on the Adenocarcinoma gastric cell line (AGS) gastric cancer cell line was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, which showed that the new 5-fluorouracil (5FU) analog, with an IC50 of 15.67 µg/mL, is more effective in inhibiting the proliferation of AGS cells after 24 h compared to both synthesized and reported 5FU. In addition, In-silico studies showed that the new 5FU derivative based on amino tetrazole, with a binding energy of -7.2 kcal/mol, exhibits greater anti-cancer activity against the BCL2 enzyme than 5FU, with a binding energy of - 4.8 kcal/mol. It is predicted that the new 5FU derivative will be effective in treating gastric and colorectal cancers. The new derivative of the 5-fluorouracil drug was characterized and identified using FTIR and NMR spectroscopy.Communicated by Ramaswamy H. Sarma.

Polyamidoamine Dendrimers Functionalized with ZnO-Chitosan Nanoparticles as an Efficient Surface for L-asparaginase Immobilization.

In this study, the third-generation polyamidoamine dendrimer was functionalized with a 5-amino-1H-tetrazole heterocycle to load the synthesis enzyme and its surface groups. Then, chitosan was attached to the dendrimer by a suitable linker, and finally, zinc oxide nanoparticles were inserted into dendrimer cavities to increase loading. FTIR, FESEM, TEM, and DLS analysis showed that this new dendrimer has specific branches, and ZnO nanoparticles were spread between the branches and connected with the branches and chitosan biopolymer. Also proved the presence of stabilized L-asparaginase enzyme and ZnO nanoparticles in the designed system. Furthermore, the extent of L-asparaginase enzyme loading and release was investigated in the laboratory with a dialysis bag. Examining the toxicity of the new third-generation polyamidoamine (PAMAM) dendrimeric nanocarrier based on chitosan-zinc oxide biopolymer (PAMAM-G3@ZnO-Cs nanocarrier) on the Jurkat cell line (human acute lymphoblastic leukemia) at pH 7.4 showed that this nanocarrier effectively encapsulates the drug L-asparaginase and slowly releases it and also preventing the growth of cancer cells. The activity of the loaded enzyme in the nanocarrier and the free enzyme was calculated. During the investigations, it was found that the enzyme attached to the nanocarrier is more stable than the free enzyme at optimal pH and temperature and at high temperatures, acidic and basic pHs. Vmax and Km values were lower for loaded enzymes. The synthesized PAMAM-G3@ZnO-Cs nanocarrier can be a promising candidate in the pharmaceutical industry and medical science for cancer treatment due to its biocompatibility, non-toxicity, stability, and slow release of L-asparaginase.

Synthesis and characterization of a novel organosilane-functionalized chitosan nanocarrier as an efficient gene delivery system: Expression of green fluorescent protein.

Semi-essential arginine amino acid was selected to synthesis an organosilane linker for modifying chitosan biopolymer. The novel organosilane linker which was chemically synthesized by reaction of arginine with 3­chloropropyl trimethoxy silane, covalently bonded to the chitosan amino group. The chemical structure of resulting nanocarrier was characterized by 1H NMR, wide-X-ray diffraction, TEM, FESEM and EDX. A maximum retardation capacity of the nanocarrier to the plox plasmid was obtained 3 at physiological pH (7.4). The mean of cell viability and cytotoxicity of the nanocarrier was determined 85% by MTT assay. In addition, the gene transfection of the nanocarrier was obtained top of 20% gene expression. The studies have shown very good DNase 1 enzyme protection of plasmid by the nanocarrier.

Synthesis and characterization of aminotetrazole-functionalized magnetic chitosan nanocomposite as a novel nanocarrier for targeted gene delivery.

In the present study, Fe3O4/chitosan biopolymer grafted to a novel organosilane modified 5-amino-1H-tetrazole, a kind of drug intermediate, was successfully synthesized by chemical modification technique and evaluated as a high potential carrier of gene delivery. The loading capacity was evaluated, and in vitro release of nanocarrier was assessed using the dialysis method. The transfection efficiency of plasmid was optimal at an N/P ratio of 3. The chemically modified chitosan showed no inherent toxicity toward the cells. The synthesized nanocarrier had enhanced release of the plasmid at physiological pH 7.4. The N-functionalized magnetic chitosan nanocarrier demonstrated its efficacy in the enhancement of gene expression in the HECK-293T cell line. Therefore, the novel magnetic N-functionalized chitosan showed promise as a highly efficient gene carrier with potential applications in cancer therapy.