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Virus-Based Nanocarriers for Targeted Drug Delivery
Published in Devarajan Thangadurai, Saher Islam, Charles Oluwaseun Adetunji, Viral and Antiviral Nanomaterials, 2022
Semra Akgönüllü, Monireh Bakhshpour, Yeşeren Saylan, Adil Denizli
Functionalization is reached via attracting the peptides, antibodies, oligonucleotides, fluorescent reagents, drug molecules, and proteins to the capsid through various chemical materials, including maleimide, N-hydroxy-succinimidyl ester, carbodiimide, and isothiocyanate. Genetically, a cysteine residue could be let into a subunit that shows a thiol-based group in the assembled surface capsid structure (Wang et al. 2002). The summary of the general bioconjugation techniques used for modification is shown in Figure 9.5 (Alemzadeh et al. 2018). A new way to conduct bioconjugation is through click-chemistry. Magnificent progress in the chemoselective ligation on the surfaces of the virus utilised click-chemistry where the virus-based nanocarriers could be coupled in an orthogonal style without using safety groups. The click-chemistry reaction is chosen for bioconjugation because is quicker, bio-orthogonal, and more easily continues than suitable NHS reactions. The other chemo-selective approach is hydrazone-ligation. All chemical materials in the drug would be immediately bioconjugated to the surface of the virus, which is very important (Pokorski and Steinmetz 2011).
Intelligent Nanomaterials for Medicine: Carrier Platforms and Targeting Strategies—State of the Art
Published in Lajos P. Balogh, Nano-Enabled Medical Applications, 2020
Georgette B. Salieb-Beugelaar, Marc Wolf, Roman Lehner, Kegang Liu, Stephan Marsch, Patrick Hunziker
Carbon nanotubes are a distinct molecular form of carbon atoms, yielding a hexagonal arrangement. Carbon nanotubes exist as single-walled and multi-walled variants [68]. Their structure, formed from layered graphite sheets, gives them extreme physical strength, 10 times as strong as steel, and unusual heat and conductivity properties [69]. Recently carbon nanotubes have attracted attention due to their use in controlled drug release as well as delivery of nucleic acids, peptides, and antibodies. Their inner core and their outer surface allow the insertion of specific payload into the small inner core, while the outer surface can be modified to achieve the necessary biocompatibility within the body or to attach targeting ligands or drug payloads [70, 71]. Gu et al. published data concerning single-walled carbon nanotubes (SWNTs) coated with doxorubicin, exhibiting a pH-responsive drug release behavior [72]. They covalently attached hydrazino-benzoic acid to the SWNTs using hydrazine as linker molecule. Doxorubicin was bound to the modified SWNTs forming hydrazone bonds with hydrazinobenzoic acid. In vitro testing of these SWNTs showed drug release upon pH change. In an acidic tumor microenvironment, this application could provide a specific drug release system.
Clinical Pharmacology of the Anti-Tuberculosis Drugs
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Gerry Davies, Charles Peloquin
Serious drug-induced liver injury occurs in ∼2% of people taking INH monotherapy for chemoprophylaxis at standard doses21 and has been associated in meta-analyses with NAT2 polymorphisms predicting slow/intermediate acetylator phenotype.22 The acetylhydrazine metabolite has been identified as a candidate toxigen which may generate additional hepatotoxins through the CYP2E1 pathway. Meta-analyses in predominantly Asian populations suggest that polymorphisms in this pathway may be associated with a higher risk of hepatotoxicity.23 Neurotoxicity of INH is believed to be related to the formation of hydrazones which inhibit enzymes requiring pyridoxal phosphate as a co-factor. The most common manifestation is sensory peripheral neuropathy, which was observed in 2%–12% of patients in early studies and is more common with higher doses, HIV co-infection, and slow acetylator status.24,25 It is reliably prevented by prophylaxis with small doses of pyridoxine (10–50 mg daily). More serious neurological side effects including encephalopathy may occur in overdose and may be counteracted by much higher doses of pyridoxine. In addition, INH is structurally related to iproniazid, one of the first monoamine oxidase inhibitors and can rarely be associated with mood disturbance. INH is also a rare cause of drug-induced systemic lupus erythematosus and of sideroblastic anemia.
Discovery of sulfonamide-tethered isatin derivatives as novel anticancer agents and VEGFR-2 inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Moataz A. Shaldam, Hadia Almahli, Andrea Angeli, Rehab Mustafa Badi, Eman F. Khaleel, Abdelrahman I. Zain-Alabdeen, Zainab M. Elsayed, Eslam B. Elkaeed, Rofaida Salem, Claudiu T. Supuran, Wagdy M. Eldehna, Haytham O. Tawfik
General preparation procedures used in synthesising the designed compounds 6a-i are shown in Scheme 1. The first step in synthesis was the preparation of benzenesulfonyl chloride 2 using thionyl chloride and chlorosulfonic acid in performing chlorosulfonation of compound 1. An excess chlorinating agent 2:1 was used to enhance the yield after 26 h. The formation of benzenesulfonamide intermediate 3 was accomplished by reacting compound 2 with ammonia using ethanol as solvent22. The synthesis of hydrazone intermediate 4 was carried out by refluxing compound 3 with hydrazine hydrate for 4 h in the presence of glacial acetic acid as catalyst and ethanol as solvent23. The target compounds 6a-i were prepared by reacting them with various isatin derivatives 5a-i in the presence of a catalytic amount of glacial acetic acid and under reflux conditions24–26.
Enhanced therapeutic efficacy of doxorubicin against multidrug-resistant breast cancer with reduced cardiotoxicity
Published in Drug Delivery, 2023
Tianyu Zhang, Nuannuan Li, Ru Wang, Yiying Sun, Xiaoyan He, Xiaoyan Lu, Liuxiang Chu, Kaoxiang Sun
Tumor microenvironment, with rapid proliferation and differentiation of cancer cells, displays various differences with normal body environment, such as lower pH, higher concentration of reducing substance glutathione (GSH), excessive expression of specific enzymes (Fathi et al., 2018), as well as the enhanced permeability and retention (EPR) effect. Based on the characteristics of tumor microenvironment, many nanoparticles have been reported to passively target tumors by EPR effect (Jin et al., 2019). More effective treatment can be achieved by using stimuli-responsive carriers like the ones with hydrazone bond. The hydrazone bond is stable under neutral conditions but easy to break under acidic or weak acidic conditions (Hu et al., 2018), so that the drugs can be effectively released at the tumor site, resulting an improved therapeutic efficacy and reduced side effect. In addition to the passive targeting delivery and stimuli-responsive release of therapeutic drugs based on the tumor microenvironment, some active targeting delivery systems are also designed based on the special characteristics of tumor cells. Folic acid receptor is a glycoprotein receptor, which has low expression in normal body cells and high expression in breast cancer cells (Choi et al., 2018). It has a high affinity for both folic acid (FA) and folic acid complex (Heo et al., 2019). Therefore, FA modification can effectively improve the active targeting effect of nano-system and deliver drugs to the tumor tissue, improving the drug accumulation at the tumor site while reducing the damage of drugs to normal body cells.
Isocoumarins: a new class of selective carbonic anhydrase IX and XII inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Mehmet Onyılmaz, Murat Koca, Alessandro Bonardi, Mustafa Degirmenci, Claudiu T. Supuran
The structurally diverse isocoumarin derivatives X(1–20) were synthesised according to the general synthetic route shown in Scheme 1. 3-Acetylisocoumarin-substituted compounds B were synthesised as previously described by some of us15. The hydrazone derivatives X(1–5) were obtained by reacting B with substituted hydrazines16. The aldehydes X(6–10) were synthesised in high yields by using the Vilsmeier-Haack procedure17. These aldehydes were condensed with barbituric acid/2-thiobarbituric acid under acid condition at reflux to produce the final derivatives X(10–20). The chemical structures of the novel isocoumarin-substituted derivatives reported here were confirmed by analytical and spectral data (see Materials and methods for details).