Synthesis, biological and electrochemical evaluation of novel nitroaromatics as potential anticancerous drugs (original) (raw)
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Journal of Medicinal Chemistry, 1991
- Chapman, J. D.; Greenstock, C. L.; Reuvere, A. P.; McDonald, E.; Dunlop, I. Radiat. Res. 1973,53, 190. Adams, G. E.; Clarke, E. D.; Flockhart, I. R.; Jacobs, R. S.; Sehmi, D. S.; Stratford, I. J.; Wardman, P.; Watts, M. E. Int. J. Radiat. Biol. 1979, 35, 133. A d m , G. E.; Flockhart, I. R.; Smithen, C. E.; Stratford, I. J.; Wardman, P.; Watts, M. E. Radiat. Res. 1976, 67, 9. Wasserman, T. H.; Philips, T. L.; van Raalte, G.; Urtasun, R. C.; Partington, J.; Koziol, D.; Schwade, J.; Gangji, D.; Strong, J. M. Br. Roberts, J. T.; Bleehen, N. M.; Workman, P.; Watson, M. I. Int. J. Radiat. Oncol. Biol. Phys. 1984, 10, 1755. Saunders, M. I.; Anderson, P. J.; Bennett, M. H.; Dische, S.; Minchington, A.; Stratford, M. R. L.; Tothill, M. Int. J. Rad i d . Oncol. Biol. Phys. 1984, 10, 1759. Adams, G. E.; Ahmed, I.; Sheldon, P. W.; Stratford, I. J. Br. J. Cancer 1984,49, 571. O'Neill, P.; Jenkins, T. C.; Stratford, I. J.; Silver, A. R. J.; Ahmed, I.; McNeil, S. S.; Fielden, E. M.; Adams, G. E. Anti-Cancer Drug Des. 1987, I, 271. Adams, G. E.; Ahmed, I.; Sheldon, P. W.; Stratford, I. J. Int. J. Radiat. Oncol. Biol. Phys. 1984, 10, 1653. Jenkins, T. C.; Naylor, M. A,; O'Neill, P.; Threadgill, M. D.; Cole, S.; Stratford, I. J.; Adams, G. E.; Fielden, E. M.; Suto, M. J.; Stier, M. A. J. Med. Chem. 1990, 33, 2508. Cole, S.; Stratford, I. J.; Adams, G. E.; Fielden, E. M.; Jenkins, T. C. Radiat. Res., in press. Dale, J. A.; Jacobs, R. S.; Wardman, P.; Watts, M. E. In Radiation Sensitizers: Their Use in the Clinical Management of Cancer, Brady, L. W., Ed.; Masson Press: New York, 1980. Walling, J. M.; Stratford, I. J.; Adams, G. E.; Silver, A. R. J.; Ahmed, I.; Jenkins, T. C.; Fielden, E. M. Int.
Turkish Journal of Biochemistry, 2014
Genotoxicity of potent antiviral 1-[(2-aminophenyl)thio]-1-phenyl-2-nitrobutane derivatives designed as drug agents [İlaç etken maddesi olarak tasarlanmış kuvvetli antiviral 1-[(2-aminofenil)tiyo]-1-fenil-2-nitrobütan türevlerinin genotoksisitesi] ABSTRACT Objective: Genotoxic potentials of six selected nitrobutane (I) derivatives designed as drug agents were tested here for the first time using umu-microplate test system. An important principle in drug development is to perform safety tests of previously determined significant drug activity in in vitro assays. This may be even more crucial than its efficiency in terms of experimental conditions, since it is important in chemotherapy to treat without risk for the patient. Methods: Umu-microplate test system is especially designed for detecting the mutagenicity of nitro compounds. 1-[(2-aminophenyl)thio]-1-phenyl-2-nitrobutane (I) derivatives involve nitro groups. Therefore umu-microplate test system has been chosen for our analysis. Evaluation of the SOS inducing activity of the tested compounds was examined with the umu-microplate test system using Salmonella typhimurium NM1011 (overexpressed NR (nitroreductase)) and S.typhimurium NM2009 (overexpressed O-At (O-acethyltransferase))strains which are sensitive to nitro compounds. Chlorophenol red-β-D-galactopyranoside (CPRG) and O-nitrophenyl-β-D-galactopyranoside (ONPG) were used as substrate in the enzyme assays and also the well-known genotoxic nitro compound, 4-nitroquinoline 1-oxide (4NQO), was the positive control in the test. Results: Although the β-galactosidase activities with using CPRG were three fold higher than ONPG, parallel results were obtained for both substrates and strains with all compounds tested. For all compounds, the induction of umuC gene expression was found to be almost the same for the strains that overexpress NR and O-At. The derivatives tested didn't caused an evident induction in both strains overexpressed NR and O-At enzymes which have a role in metabolic activation mechanism of nitro compunds. Conclusion: Our study showed that, 1-[(2-aminophenyl)thio]-1-phenyl-2-nitrobutane derivatives have no genotoxic effects in this test system. This result is a very important data making them a potential drug candidate.
Chemical Research in Toxicology, 2008
Interest in DNA binding drugs has increased in recent years due to their importance in the treatment of genome-related diseases, like cancer. A new family of water-soluble DNA binding compounds, the benzothiazolo[3,2-a]quinolinium chlorides (BQCls), is studied here as potential candidates for chemical treatment of solid tumor cells that may encounter low-oxygen environments, a condition known as hypoxia. These compounds are good DNA intercalators; however, no studies have been made of these compounds under hypoxic conditions. This work demonstrates the importance of the nitro-functionality in the DNA binding of 3-nitro-10-methylbenzothiazolo[3,2-a]quinolinium chloride (NBQ-91), which possesses nitro-functionality, and 10-methylbenzothiazolo[3,2-a] quinolinium chloride (BQ-106), which does not. Both NBQ-91 and BQ-106 have similar noncovalent binding affinity toward DNA. Dialysis experiments show that NBQ-91 binds DNA under N 2saturated conditions with increasing concentrations of reducing agent, presumably due to reduction of the nitro-functionality. Conversely, because of the lack of nitro-functionality, the presence of a reducing agent had no effect on BQ-106 binding to DNA under both aerobic and N 2 -saturated conditions. Clonogenic assays were performed to determine the quinolinium chloride cytotoxicities under both aerobic (95% air and 5% CO 2 ) and hypoxic (80% N 2 and 20% CO 2 ) conditions. The calculated ratios of cellular toxicity under aerobic to hypoxic conditions caused by the same concentration of test agent (CTR values) show greater levels of cell death under hypoxia than under aerobic conditions for mitomycin C (MC) (CTR = 0.7 at 1 µM) and NBQ-91 (CTR = 0.4 at 200 µM) than for BQ-106 (CTR = 1.0 at 200 µM), which agreed with the previously reported data for MC and confirmed the importance of nitro-functionality for reactivity under hypoxic conditions. There was no correlation between noncovalent binding affinity constants and their cytotoxicity under hypoxic conditions. Adduct formation between the NBQ-91 and 2′-dG was also assessed by reacting 2′-dG or DNA with NBQ-91 and BQ-106 under N 2 -saturated conditions in the presence of hypoxanthine and xanthine oxidase (HX/XO). DNA covalent adduct formation was analyzed by two techniques: LC-ESI-MS and Sephadex size exclusion column. LC-ESI-MS results clearly indicate the formation of a prominent molecular ion at masses of 266.0 and 530.58 Da, corresponding to the [M + H] +2 and [M] + molecular ions of the monitored 2′-dG-NBQ-91 adduct. Results from the Sephadex size exclusion chromatography support these findings because the NBQ-91 elution percentage increases in the presence of HX/XO due to the reduction of the nitro-functionality, which results in covalent binding to DNA. This study reports evidence of the DNA binding capacity of this bioreductive drug. The preferential N 2 -saturated over aerobic conditions for DNA binding makes NBQ-91 a potential bioreductive compound for hypoxic cell killing.
Arabian Journal of Chemistry, 2020
Three 2-arylpiperidinyl-1,4-naphthoquinone derivatives were synthesized and evaluated in vitro to determine their cytotoxicity on cancer and normal cell lines. In order to establish their possible action mechanism, the electrochemical behaviour of these quinones was examined using cyclic voltammetry (CV) as technique by using a three-electrode setup: a glassy carbon, Ag/AgCl (in 3 M KCl), and platinum wire as working, reference, and counter electrodes, respectively. Kinetic studies were done to determine the control of the reduction reaction and the number of transferred electrons in the process. Furthermore, the addition of dsDNA to the quinone solutions allowed for the observation of an interaction between each quinone and dsDNA as the current-peaks became lower in presence of dsDNA. Otherwise, motivated to support the aforementioned results, electronic structure calculations at the TPSS-D3/6-31+G(d,p) level of theory were carried out in order to find the most favourable noncovalently bonded complexes between quinones and DNA. Noncovalent complexes formed between DNA and 2-arylpiperidinyl-1,4-naphthoquinones and stabilized by p-stacking interactions along with the well-known hydrogen-bonded complexes were found, with
European Journal of Medicinal Chemistry, 2008
A series of amidino-substituted benzimidazoles, related to furyl-phenyl-and thienyl-phenyl-acrylates, naphthofurans and naphthothiophenes were prepared, their antitumor evaluation and interactions with ct-DNA have been investigated. All tested compounds show differential and strong antitumor activity without apparent difference depending on their structures. Interestingly, the MCF-7 tumor cell line is highly sensitive to all compounds. Compounds 6e9 showed noticeable selectivity in regard to normal fibroblasts (WI 38). Compounds 4e9 interact with ct-DNA by more binding modes, whose mutual distribution is dependent on the compound/DNA ratio. The ''acyclic'' 4e6 and ''cyclic'' compound 7 interact mostly within the minor groove of DNA, although partial intercalation of 6 and 7 cannot be excluded. The ''cyclic'' compounds 8 and 9 intercalate between DNA base pairs at high excess of DNA over compounds.
Turkish Journal of …, 2006
The N-alkyl derivatisation and photochemical dimerisation of 3 o-, m-, and p-nitro substituted 4azachalcones (1-3) yielded 3 new o-, m-, and p-nitro substituted (E)-N-decyl-4-azachalconium bromides, (2E)-1-(2-nitrophenyl)-3-(N −decyl-4-pyridinium bromide)-2-propen-1-one (4), (2E)-1-(3-nitrophenyl)-3-(N-decyl-4-pyridinium bromide)-2-propen-1-one (5), and (2E)-1-(4-nitrophenyl)-3-(N-decyl-4-pyridinium bromide)-2-propen-1-one (6), and 3 new dimers in solution, (1β,2α)-di-(3-nitrobenzoyl)-(3β,4α)-di-(4-pyridinyl)cyclobutane (7), (1β,2α)-di-(4-nitrobenzoyl)-(3β,4α)-di-(4-pyridinyl)cyclobutane (8a), and (1β,2β)-di-(4-nitrobenzoyl)-(3β,4α)-di-(4-pyridinyl)cyclobutane (8b), stereoselectively. The monomeric compounds showed good antimicrobial activity against test microorganisms. The most sensitive microorganisms were Gram-positive bacteria. The monomers also showed high antioxidant activity, while the dimerisation products 7-8a,b were less active. Compound 6 was found to have similar or even higher activity when compared to the standard antioxidants Trolox r and vitamin C, respectively. The possible dimerisation products of compounds 1-3 were calculated theoretically. Experimental and theoretical calculations showed that δ-truxinic type dimer is the most stable isomer.
Polyhedron, 2012
In this work, some 2-phenyl quinoline-4-carboxamide derivatives (5a-j) were synthesized via base catalyzed Pfitzinger reaction of isatin and acetophenone followed by C-N coupling reaction using POCl3 and assessed them for their in vitro antimicrobial and anticancer activity. The structure of newly synthesized compound were established by FT-IR, 1 H & 13 C NMR and Mass spectrometric analysis. The synthesized carboxamides were subjected to preliminary in vitro antibacterial activity as well as for antifungal activity. Results of antibacterial activity were compared with standard antibacterial (ciprofloxocin) and antifungal (fluconozole). Among the tested compounds, 5d, 5f and 5h exhibited promising activity with zone of inhibition ranging from 10 to 25 mm. Further, the anticancer activity determined using MTT assay against two cancer cell lines. Compounds 5b, 5d, 5f and 5h showed good anticancer activity among all the other derivatives. In order to correlate the in vitro results, in silico ADME and Molecular docking studies were carried out for (5a-j). ADME properties results showed that all the compounds obey rule of Five rule except 5a, 5e and 5g compound. Molecular docking studies of the synthesized compounds showed good binding affinity through hydrogen bond interactions with key residues on active sites as well as neighboring residues within the active site of chosen target proteins viz. antibacterial, antifungal and anticancer. Comparison of both results of in silico as well as in vitro investigation suggests that the synthesized compounds may act as potential antimicrobial as well as anticancer agents.
The interaction of the antiparasitic drug nitazoxanide (NTZ) with salmon sperm double strand deoxyri-bonucleic acid (ss-ds-DNA) has been studied using cyclic voltammetry (CV) and differential pulsevoltammetry (DPV) at screen printed carbon electrode (SPCE). NTZ shows two irreversible oxidationpeaks measured in 0.02 M phosphate buffer (pH 4.0 and 7.4). UV/Vis spectroscopy was also employedto probe the interaction between NTZ and ss-ds-DNA. From the CV data, the diffusion coefficients werefound as 5.1 × 10−7and 4.9 × 10−9cm2s−1for NTZ and NTZ-DNA, respectively. Based on the CV and spec-troscopic results, the binding constant between NTZ and DNA was calculated to be 4.1 × 105M−1and5.0 × 105M−1, respectively. The interaction as a sum of intercalation and groove binding modes was con-cluded. A procedure for the differential pulse voltammetric determination of NTZ at a screen-printedelectrode surface modified with the ss-ds-DNA layer was also described. The method was applied for thedetermination of NTZ in spiked serum.