China
Africa
Explore chapters and articles related to this topic
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
A substituted benzoquinone ring has been employed as an “anchor” for aziridine rings in the experimental agents AZQ and BZQ. The aziridine moieties are deactivated by the withdrawal of electrons from their nitrogens into the quinone carbonyl groups via the six-membered ring. These molecules have been employed as experimental bioreductive prodrugs because reduction of the quinone ring to either the semiquinone or the hydroxyquinone species reverses the electron flow, thus increasing the basicity of the aziridine nitrogens which allows them to become activated via protonation. No benzoquinone agents of this type have yet been approved for clinical use.
The Modification of Cysteine
Published in Roger L. Lundblad, Chemical Reagents for Protein Modification, 2020
A derivatization procedure that has proved useful in the primary structure analysis of protein has been the reaction of ethyleneimine (Figure 58) with sulfhydryl groups in proteins.104 This reaction produces S-aminoethyl cysteine which provides an additional point of tryptic cleavage in proteins.105 With bovine pancreatic ribonuclease A, with a 1/100 ratio of trypsin at pH 8.0, 83% cleavage of arginyl and lysyl bonds was obtained while 56% cleavage was obtained at S-aminoethyl cysteine. This chemistry has been used to introduce a dansyl label into oncomodulin via modification of a cysteinyl residue with dansylaziridine (Figure 59).78 Since the aziridines are photosensitive compounds (see Chapter 16), reaction proceeded in the dark. A 100-fold molar excess of reagent (dissolved in either dimethylformamide or dimethylsulfoxide) at pH 7.5 (Tris or HEPES) was used. The reaction was allowed to proceed for 16 to 20 h with rocking (most of the dansylaziridine is insoluble) and reagent removed by centrifugation.
Identification of proper herbs
Published in C. P. Khare, Evidence-based Ayurveda, 2019
Taalisha still remains a drug of disputed source. Abies webbiana and Taxus wallichiana both are known as Taalisha patra. Two samples of needles and twigs from two different locations of central Nepal gave alpha-pinene 3.0, 10.3; fascile 3.5, 9.3; beta-pinene 5.1, 3.3; limonene 6.1, 2.3; bornyl acetate 4.2, 15.5; and carvone 5.8, 0.75%, respectively. Leaves obtained from Sikkim-Himalayan region gave a bioflavonoid, abiesin; two glycosides, methylbetuloside, and betuloside; n-triacontanol and beta-sitosterol. A new alkaloid, 1-(4’ methoxyphenyl)-aziridine was isolated.
Exploitation of the Ugi–Joullié reaction in drug discovery and development
Published in Expert Opinion on Drug Discovery, 2019
Stefano Gazzotti, Giulia Rainoldi, Alessandra Silvani
Alongside the synthesis of peptidomimetics and depsipeptides, vast libraries of drug-like products are also reported in the literature and discussed in this review. Three-, five- and seven-membered cyclic imines were employed as starting materials, ending up in a great variety of nitrogen-containing heterocycles, such as highly functionalized aziridine, tiazolidine and hydroazepine derivatives. All reported multicomponent reactions were characterized by mild conditions, good yields and high diastereoselectivity. No doubt, the easy and cheap access to a vast array of Ugi-Joulliè starting components (carboxylic acids and isocyanides, besides cyclic imines) proves to be a key element for the fruitful exploitation of this reaction in the field of drug discovery.
Aromatic sulphonamides of aziridine-2-carboxylic acid derivatives as novel PDIA1 and PDIA3 inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
D. Zelencova-Gopejenko, V. Andrianov, I. Domracheva, I. Kanepe-Lapsa, M. Milczarek, M. Stojak, K. Przyborowski, F. A. Fedak, M. Walczak, K. Kramkowski, J. Wietrzyk, S. Chlopicki, I. Kalvins
Aziridines, in general, are alkylating agents useful as anti-cancer medicines (thiotepa, mitomycin C, etc.). It is believed that protonated forms of aziridines mainly alkylate nucleobases1. Furthermore, aziridines also react with the cysteine thiol group of proteins, and this reaction is highly specific at slightly alkaline pH values. However, in aqueous solutions, the competing side reaction is hydrolysis2. Electron withdrawing substituents decrease the electron density on aziridine ring atoms, leading to a lower reactivity of such aziridine derivatives towards nucleic acids and increasing their selectivity for thiolate anions3.
Significant role of cationic polymers in drug delivery systems
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Masoud Farshbaf, Soodabeh Davaran, Amir Zarebkohan, Nasim Annabi, Abolfazl Akbarzadeh, Roya Salehi
Poly(ethyleneeimine) (PEI), a none-degradable polymer comprising primary, secondary and tertiary amino groups which is one of the most commonly employed cationic polymers in various industries. PEI can be obtained in two various structures: (i) linear PEI (LPEI) is a solid form of PEI and (ii) branched PEI (BPEI) is a highly viscous liquid at the room temperature. LPEI contains primary and secondary amino groups, while BPEI, in addition to primary and secondary groups, also possesses tertiary amino groups (with ratio of 1:2:1) which makes BPEI more stable and suitable transfection vector [107]. It is worth noting that, at physiological conditions 25% of these amino groups are protonated which gives PEI high buffer capability that could be beneficial in endosomal escape mechanisms. Brissault et al. [108] synthesized LPEI by hydrolysis and/or reduction of poly(2-ethyl-2-oxazoline) (PEtOXZ) (Figure 12(A)). A mixture of PEtOXZ (1 g), hydrochloric acid (11 ml, 37%) and 8 ml water was heated at 110 °C for 3 h. After solvent evaporation, the obtained mixture was dissolved in water and pH was adjusted to 9–10 by adding a proper amount of NaOH. Then the aqueous phase was vaporized, the residue washed with methylene chloride and consequently, the organic layer (Na2SO4) dried and vaporized. Based on results, yield of the polymer was 320 mg (71%) [108]. In another study, Harpe et al. [109] used acid-catalyzed polymerization of aziridine for the synthesis of BPEI (Figure 12(B)). First, aziridine (5 ml) were dissolved in 50 ml distilled water and 0.5 ml of 32% (w/v) hydrochloric acid (HCl) were added to the solution, then the flask was sealed and submerged in oil bath in 65 °C and kept for 24 h. NaOH was added to the mixture in order to neutralization process and then water was vaporized and the obtained polymer was dried under vacuum for 24 h [109].