Chemical Hybridization Approaches Applied to Natural and Synthetic Compounds for the Discovery of Drugs Active Against Neglected Tropical Diseases
Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay in Medicinal Chemistry of Neglected and Tropical Diseases, 2019
Very good results in term of both selectivity and activity were obtained when the triazine ring was hybridized with the quinazoline moiety (79 and 80, Figure 20) (Sharma et al. 2013). The preparation was a simple functionalization of a previously prepared quinazoline ring with cyanuric chloride, and a systematic substitution of the Cl atoms with different amines. The same quinazoline nucleus was hybridized with peptides thus obtaining 9 promising compounds. The triazine hybrids were both active as antipromastigotes and antiamastigotes with a low cytotoxicity and a very good SI. The hybrid peptide 81 bearing a ferrocene moiety was not active at all on promastigotes, while it strongly affected amastigote proliferation with a SI > 548. However, these hybrids, that were very promising even in in vivo studies in the golden hamster model, strongly reacted with blood proteins with a static and dynamic quenching of intrinsic fluorescence. Tetrahydroquinazoline-triazine hybrid compounds.
Herbicides
Frank A. Barile in Barile’s Clinical Toxicology, 2019
Table 29.3 summarizes the chemical and toxicological properties of selected miscellaneous herbicides. The triazines, substituted ureas, and nitroaromatic and chloroanilide classes are frequently used as contact, preemergence, and select herbicides. Their low to moderate toxicity to humans and animals makes them suitable for agricultural, industrial, and household utility. Their structural commonalities (highlighted in blue in Figure 29.3), such as the nitrogen moieties, explain their relative effectiveness and selective toxicology (Figure 29.3). Structures of selected triazine, substituted urea, and nitro aromatic herbicides. Their structural similarities, highlighted in blue, such as the triazine, urea, and dinitro moieties (for atrazine, monuron, and dinoseb, respectively), account for the relative effectiveness and selective toxicity of nitrogen-containing molecules.
Agrochemicals: A Brief Overview
Dongyou Liu in Handbook of Foodborne Diseases, 2018
Atrazine is an herbicide of the family of triazines, extensively used for control of broad-leaf weeds and certain grasses (37). Their herbicidal action is due to inhibition of photosynthesis, a process unique to plants (11,37), and all triazines have low acute oral and dermal mammalian toxicity (LD50 = 1–2 g/kg). Animal studies have suggested that atrazine may be carcinogenic, as mammary tumors were reported in female Sprague-Dawley rats (37,38); however, such an effect may involve a primary action on pituitary luteinizing hormone seen only at high doses, and it may thus have a threshold (37). Epidemiological studies of triazine herbicides and cancer have provided inconclusive results (39,40), and atrazine is classified by IARC as a Group 3 carcinogen (not classifiable as to its carcinogenicity to humans).
Discovery of novel enasidenib analogues targeting inhibition of mutant isocitrate dehydrogenase 2 as antileukaemic agents
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Ahmed F. Khalil, Tarek F. El-Moselhy, Eman A. El-Bastawissy, Rasha Abdelhady, Nancy S. Younis, Mervat H. El-Hamamsy
Initially, the anticancer effects of target compounds have been assessed at a single (10 μM) dose. The obtained data have been reported as mean-graph of the percent growth (G%) of the treated cancer cells. Percentage growth inhibition (GI%) is calculated (100 − G%) and pronounced in Table 1. Inspection of in vitro antitumor screening data revealed that our s-triazine derivatives exposed variable anticancer activity ranging from low, moderate, to high potency. Preliminary examination of NCI data showed that compounds in series (I) with morpholine head and their corresponding analogues in series (II) with piperidine moiety demonstrated an overall comparable activity as reported in Figure 5. Target compounds in series (III) with manipulated linkers disclosed lower potency. Superiorly, eight s-triazine derivatives from the three series (6a, 6c, 6d, 7a, 7g, 7i, 7l, and 8b) have shown potent broad-spectrum anticancer activity against most the examined cell lines, whereas most of the remaining triazine derivatives, 20 derivatives, have exerted selective anti-proliferative actions towards certain cancer cell lines (Supplementary). The GI% exerted by the examined s-triazine derivatives 6a, 6c, 6d, 7a, 7g, 7i, 7l, and 8b have been listed in Table 1.
Erythema multiforme following exposure to the herbicide atrazine
Published in Baylor University Medical Center Proceedings, 2021
Madeline Frizzell, Nhan M. Nguyen, Sonal A. Parikh, Maya Sinai, Leonard Goldberg
Atrazine is a triazine drug, belonging to a class of nitrogen-containing heterocycles. It works by binding to plastoquinone-binding protein in photosystem II, a protein that animals lack, and thereby inhibiting the electron transport process.9 The plant dies as a result of photosynthesis inhibition.9 A study to assess the percutaneous absorption of atrazine in human skin found that 16.4% of the applied dose was absorbed, indicating its permeability potential.10 Many anticonvulsants also contain aromatic amine structures like atrazine and are well-known causes of erythema multiforme and Stevens-Johnson syndrome. Lamotrigine, phenytoin, and carbamazepine all contain aromatic amine groups, which have been more commonly related than others to the development of Stevens-Johnson syndrome and toxic epidermal necrolysis.11 However, the relationship between the aromatic amine structure and the development of these hypersensitivity disorders is not understood.11
Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Justyna Magdalena Hermanowicz, Anna Szymanowska, Beata Sieklucka, Robert Czarnomysy, Krystyna Pawlak, Anna Bielawska, Krzysztof Bielawski, Joanna Kalafut, Alicja Przybyszewska, Arkadiusz Surazynski, Adolfo Rivero-Muller, Mariusz Mojzych, Dariusz Pawlak
Therefore, the search for new lead structures and chemical entities for the development of new effective anticancer agents is an increasingly important task in medicinal chemistry. This trend of global research includes work on the use of 1,2,4-triazine scaffold as a source for the design of biologically relevant molecules with well-known broad biological applications5. Thus, the 1,2,4-triazine ring is an eminent structural motif found in plentiful natural and synthetic biologically active compounds6. Among the known various biological activities of 1,2,4-triazines and their related benzo- and heterofused derivatives, antitumor activity deserves special attention. Recently, a few reviews on the chemistry and the biological properties of this class of compounds have been published7–9.
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