- Synthesis of novel hybrid molecules from precursors with known antiparasitic activity
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Three novel new compounds derived from antiparasitic precursors have been synthesized and tested for their antiamoebic and antigiardial activities. The condensation of 2-(2-methyl-5-1H-nitroimidazolyl)ethylamine (6) with 5-nitro-2-furylacrylic acid (7) gave 3-(5-nitrofuran-2-yl)-N-[2-(5- nitroimidazol-1-yl)ethyl]acrylamide (8). Condensation of 7 with 7-chloro-4-(piperazin-1-yl)quinoline (9) afforded 1-[4-(7-chloroquinolin-4-yl) piperazin-1-yl)-3-(5-nitrofuran-2-yl)propenone as a mixture of two isomers; 10-a (the E-isomer) and 10-b (the Z-isomer). In addition, the reaction of 9 with 1-(2-bromoethyl)-2-methyl-5-nitroimidazole (11) in the presence of K 2CO3 and NaI yielded 7-chloro-4-(4-[2-(5-nitroimidazol-1- yl)ethyl]-piprazin-1-yl)quinoline (12). On the basis of preliminary screening data for these new compounds, compound 12 exhibited potent lethal activities against Entamoeba histolytica and Giardia intestinalis; its IC50 ( about 1 μM) was lower, at least by a factor of five, compared to the standard drug, metronidazole. In addition, the IC50 of compound 12 against the tested parasites is 600 times below that against Hep-2 and Vero cells. Compounds 8 and 10-a also exhibited potent or moderate antiamoebic and antigiardial activities with IC50 values of about 5.5 μM, and 140 μM, respectively, against the tested parasites. These two hybrid molecules, 8, 10-a, were also non-cytotoxic at the lethal concentrations against the parasites.
- Saadeh, Haythem A.,Mosleh, Ibrahim M.,Mubarak, Mohammad S.
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- Synthesis and evaluation of a boronated nitroimidazole for boron neutron capture therapy
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We postulated that nitroimidazoles, previously used for radiosensitizing solid tumors, may be interesting templates as carriers of 10B for boron neutron capture therapy. To test this hypothesis, we synthesized a 10B- enriched nitroimidazole, 1-[2-[(undecahydro-closo-dodecaborato)thio]ethyl]- 2-methyl-5-nitroimidazole (imidocaptate), by coupling the Cs salt of BSH (Cs210B12H11SH) with 1-(2-bromoethyl)-2-methyl-5-nitroimidazole followed by purification of the adduct. Imidocaptate was taken up by V-79 cells in culture and showed no inherent toxicity under euoxic conditions up to 1.05 mM (126 μg of 10B/mL of culture medium). Imidocaptate showed a dose-dependent decrease in D(o) when the treated cells were irradiated with a thermal neutron beam. At the highest dose tested (126 μg of 10B/mL of culture medium), the ratio of control to sample D(o) values was 2.6 for both linear quadratic and single-hit multitarget models. At 33 μg of 10B/mL, imidocaptate showed a control/treated Do ratio (1.5) equal to that observed with the disulfide form of BSH at 28 μg of 10B/mL. Compared to BSH and its disulfide, the reduced toxicity and equipotency of imidocaptate suggest that this agent may be useful for boron neutron capture therapy of cancer.
- Swenson, David H.,Laster, Brenda H.,Metzger, Robert L.
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- Crystal Habit Modification of Metronidazole by Supramolecular Gels with Complementary Functionality
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A series of bis(urea) compounds with complementary functional groups similar to the pharmaceutical drug metronidazole and a structural isomer isometronidazole have been synthesized. The gelation properties of these compounds were studied in various solvent/solvent mixtures. The mechanical strength of the isomeric gelators was compared using rheology, and the morphologies of the xerogels were analyzed by scanning electron microscopy. These gels were used as media for metronidazole crystallization resulting in a marked habit modification of the metronidazole crystals in the drug-mimicking gels. However, crystallization in the nonmimetic isomeric gel resulted in morphologies similar to the solution state. These results indicate that the drug-mimetic gels interact with the surface of the drug crystal giving rise to new morphologies.
- Jayabhavan, Sreejith Sudhakaran,Steed, Jonathan W.,Damodaran, Krishna K.
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p. 5383 - 5393
(2021/08/23)
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- Alkylated/aminated nitroimidazoles and nitroimidazole-7-chloroquinoline conjugates: Synthesis and anti-mycobacterial evaluation
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The success in exploring anti-tubercular potency of nitroimidazole and quinoline, the core moieties of recently approved anti-tubercular drugs instigated us to synthesize a series of alkylated/aminated 2-methyl-5-nitroimidazoles and nitroimidazole-7-chloroquinoline conjugates and to evaluate them for their activities against Mycobacterium tuberculosis as well as for their cytotoxicity towards the J774 murine macrophage cell line. Although the synthesized compounds did not surpass the activity of the standard drug Isoniazid, they have appreciable activities with minimal cytotoxicity. The synthesized nitroimidazole-7-chloroquinoline conjugate, 11c, having butyl chain as linker, proved to be the most potent among the series with an MIC50 value of 2.2 μg/mL.
- Shalini,Viljoen, Albertus,Kremer, Laurent,Kumar, Vipan
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p. 1309 - 1312
(2018/03/21)
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- A treating agent temp.and for water treatment and preparation method thereof
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The invention relates to a biological slime treating agent for water treatment and a preparation method of the biological slime treating agent. The biological slime treating agent comprises the following components in percentage by weight: 5-30% of 1-(2-thiocyano)ethyl-2-methyl-3-benzyl-5-nitroimidazole, 5-10% of N,N-bis(dodecyldimethyl)-3-oxa-1,5-pentadiammonium dichloride, 5-10% of dithiocyanomethane, 1-10% of isothiazolinone, 1-10% of organochlorine, 5-40% of a solvent and the balance of water. The preparation method of the biological slime treating agent is as follows: at room temperature, adding 1-(2-thiocyano)ethyl-2-methyl-3-benzyl-5-nitroimidazole, N,N-bis(dodecyldimethyl)-3-oxa-1,5-pentadiammonium dichloride and water into a reactor, adjusting the pH value to less than 6 with hydrochloric acid, adding an alcohol solvent, uniformly stirring, adding isothiazolinone and organochlorine and stirring until isothiazolinone and organochlorine are completely dissolved to obtain the biological slime treating agent. The biological slime treating agent has good bactericidal property, can be widely used in industrial circulating water treatment and especially can be suitable for controlling the breeding of bacteria such as SRB in an oily wastewater system of an oilfield.
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Paragraph 0029
(2017/03/17)
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- Novel 1,3,4-oxadiazole thioether derivatives targeting thymidylate synthase as dual anticancer/antimicrobial agents
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A series of novel 1,3,4-oxadiazole thioether derivatives (compounds 9-44) were designed and synthesized as potential inhibitors of thymidylate synthase (TS) and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 18 bearing a nitro substituent exhibited more potent in vitro anticancer activities with IC50 values of 0.7 ± 0.2, 30.0 ± 1.2, 18.3 ± 1.4 μM, respectively, which was superior to the positive control. In the further study, it was identified as the most potent inhibitor against two kinds of TS protein (for human TS and Escherichia coli TS, IC50 values: 0.62 and 0.47 μM, respectively) in the TS inhibition assay in vitro and the most potent antibacterial agents with MIC (minimum inhibitory concentrations) of 1.56-3.13 μg/mL against the tested four bacterial strains. Molecular docking and 3D-QSAR study supported that compound 18 can be selected as dual antitumor/antibacterial candidate in the future study.
- Du, Qian-Ru,Li, Dong-Dong,Pi, Ya-Zhou,Li, Jing-Ran,Sun, Jian,Fang, Fei,Zhong, Wei-Qing,Gong, Hai-Bin,Zhu, Hai-Liang
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p. 2286 - 2297
(2013/05/09)
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- Synthesis of nitroimidazole derived oxazolidinones as antibacterial agents
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A series of N-alkylated derivatives of nitroimidazolyl oxazolidinones 6a-i with various substituent at N-1 position of the nitroimidazole were synthesized and their in-vitro antibacterial activities were evaluated against several Gram-positive and Gram-ne
- Varshney, Vandana,Mishra, Nripendra N.,Shukla, Praveen K.,Sahu, Devi P.
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scheme or table
p. 661 - 666
(2010/04/04)
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- Metronidazole derivatives as antiparasitic agents
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2-methyl-5-nitro-imidazolyl compounds with the general formula I, II or III: wherein one of the groups R1, R2, R3, R4, R5 is selected from an aldehyde and a 5- or 6-membered aromatic heterocylic group
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Page/Page column 10
(2009/08/16)
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- The syntheses and crystal structures of metronidazole-derived compounds
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Metronidazole (MET-OH), widely used as an antibacterial agent, is found to have some side effects on human bodies. Due to these disadvantages, people have been looking for its modification compounds for substituents. In this article, four MET-OH derivatives were designed, prepared, and structurally characterized by single crystal X-ray diffraction. These compounds are MET-OTs (1), MET-Br (2), MET-Cl (3), and MET-I (4). X-ray structure analyses revealed that, 1 crystallized in the monoclinic system with space group P2 1 /c, with a = 16.1178, b = 7.5473, c = 13.4161 A, V = 1520.3 A3, β = 111.3210o and Z = 4. 2 crystallized in the monoclinic system with space group P2 1 /c, with a = 12.079, b = 11.089, c = 6.380 A, V = 847.1 A3, β = 97.57o and Z = 4. 3 crystallized in the monoclinic system with space group P2 1 /c, with a = 12.098, b = 11.007, c = 6.295 A, V = 830.3 A3, β = 97.886o and Z = 4. 4 crystallized in the triclinic system with space group P1, with a = 6.192, b = 7.740, c = 10.001 A, V = 457.9 A3, α = 89.073, β = 86.903, γ = 73.097 o and Z = 2. In this article, metronidazole-derived compounds were prepared and structurally characterized by single crystal X-ray diffraction [Figure not available: see fulltext.]
- Li, Huan-Qiu,Xiao, Zhu-Ping,Fang, Rui-Qin,Zhu, Hai-Liang
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p. 461 - 466
(2008/09/21)
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- Hypoxia-Selective Antitumor Agents. 10. Bis(nitroimidazoles) and Related Bis(nitroheterocycles): Development of Derivatives with Higher Rates of Metabolic Activation under Hypoxia and Improved Aqueous Solubility
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A series of analogues of the prviously described compound N--4-(2-nitroimidazol-1H-yl)butanamide (4), a novel hypoxic cell cytotoxin and radiosensitizer, have been prepared and evaluated for hypoxia-selective cytot
- Hay, Michael P.,Lee, Ho H.,Wilson, William R.,Roberts, Peter B.,Denny, William A.
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p. 1928 - 1941
(2007/10/02)
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- Process for production of 5-nitroimidazole derivatives
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A process for preparing 5-nitroimidazole compounds of STR1 where R and R1 are each alkyl from 1 to 4 carbon atoms, A is oxygen and n is 1, allowing for improved yields of the final products, is described.
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