Acriflavine modification of nucleic acid formation, mutation induction and survival in ultraviolet light exposed bacteria

Doudney, C. O.; White, Billie F.; Bruce, Betty J.

doi:10.1016/0006-291x(64)90105-6

Cited by 32 publications

(7 citation statements)

References 3 publications

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“…There is some evidence related to the DNA interacting property of Acridine ring containing compounds that limit its widespread use . UV exposure of E. coli cells in the presence of micromolar level of Acriflavine (1 μg/mL = 3.8 μM) results in higher rate of cell death, mutation frequency, and blockage of DNA, RNA, and protein synthesis . No measurable incidence of mutation in non-UV exposed ACF treated cells was found in the same study .…”

Section: Discussionmentioning

confidence: 62%

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Potent Antimalarial Activity of Acriflavine In Vitro and In Vivo

et al. 2014

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Malaria continues to be a major health problem globally. There is an urgent need to find new antimalarials. Acriflavine (ACF) is known as an antibacterial agent and more recently as an anticancer agent. Here, we report that ACF inhibits the growth of asexual stages of both chloroquine (CQ) sensitive and resistant strains of human malarial parasite, Plasmodium falciparum in vitro at nanomolar concentration. ACF clears the malaria infection in vivo from the bloodstreams of mice infected with Plasmodium berghei. Interestingly, ACF is accumulated only in the parasitized red blood cells (RBCs) and parasite specific transporters may have role in this specific drug accumulation. We further show that ACF impairs DNA replication foci formation in the parasites and affects the enzymatic activities of apicoplast specific Gyrase protein. We thus establish ACF as a potential antimalarial amidst the widespread incidences of drug resistant Plasmodium strains.

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Section: Discussionmentioning

confidence: 62%

“… 33 No measurable incidence of mutation in non-UV exposed ACF treated cells was found in the same study. 33 The increased lethality and mutation rate in the presence of ACF may occur due to the interaction of ACF with UV damage site (thymine dimer, which is otherwise repairable). Therefore, ACF may not be mutagenic by itself.…”

Section: Discussionmentioning

confidence: 63%

Potent Antimalarial Activity of Acriflavine In Vitro and In Vivo

et al. 2014

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“…Acriflavine and acridine orange increase the lag in DNA synthesis and decrease the rate of thymine dimer excision (19). Acriflavine (1 ,ug/ ml) strongly inhibits DNA, ribonucleic acid, and protein synthesis (4). We studied the effect of caffeine and acriflavine on the rate of thymine dimer excision in E. coli B/r T- (Fig.…”

Section: Methodsmentioning

confidence: 99%

Mechanism of Caffeine Enhancement of Mutations Induced by Sublethal Ultraviolet Dosages

1968

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Certain chemical compounds increase mutation frequency of Escherichia coli B/r significantly when used in conjunction with nonlethal ultraviolet (UV) dosages. Studies were done to elucidate the mechanism of this enhancing mutational effect. Dark survival curves showed that 500 ,ug of caffeine per ml in the postirradiation medium markedly decreased survival to 60 ergs/mm2 of UV in strain B/r. Caffeine did not markedly decrease survival to UV in strain B/r WP-2 hcr-. At least 90% of the mutations induced to streptomycin resistance by UV and 85 % of those induced by UV with caffeine could be photoreversed. Experiments with thymine analogues suggested that thymine dimerization at the streptomycin locus was the primary premutational photoproduct induced by sublethal UV dosages. Caffeine did not interfere with the photoreversal of induced mutants, indicating that it probably does not bind to the photoreactivating enzyme or to a UV-induced lesion in the DNA. Addition of DNA or irradiated DNA with 500 ,g of caffeine per ml resulted in no loss of the caffeine activity. The excision of UV-induced thymine-containing dimers from E. coli B/r Twas investigated in the presence and absence of caffeine. Our results indicated that caffeine prevents excision of thymine dimers, presumably by binding to the excising enzyme. This binding results in an impairment of repair, which produces the increase in mutant numbers. Caffeine, theophylline, and theobromine, as well as acridine dyes, increase the frequency of mutations induced by lethal and sublethal ultraviolet (UV) light when they are added to the postirradiation medium of Escherichia coli strain B/r (3, 14, 23, 29, 30). Bacterial killing is increased when bacteria irradiated with lethal and sublethal dosages are plated on a medium containing acriflavine (1, 7, 30) or caffeine (7, 17, 29). These compounds decrease the survival of UV-irradiated phage by inhibiting host cell reactivation (5). The increase in both killing and mutation can be attributed to inhibition of a "dark repair" process that repairs UV photoproducts in the irradiated bacteria. Irradiation of bacteria with high dosages of UV light produces a variety of pyrimidine dimers in the deoxyribonucleic acid of these organisms (DNA) (21). Pyrimidine dimers can be repaired either by photoreactivation, in which the photoreactivating enzyme splits dimers in situ (35), or by excision of pyrimidine dimers from the DNA in the dark (2, 20, 25). Numerous UVsensitive mutants of E. coli have been isolated 198 Vol. 96, No. I

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“…Likewise, it has also been documented that acriflavine overturns the propagation of tumour cells. The anti-tumour and anticancer effects of acriflavine have been reported in a variety of biological systems [ 4 , 5 ]. The identification of acriflavine as an active papain-like protease inhibitor for countering COVID-19 caused by SARS-CoV-2 is promising and essential in the sense that it inhibits viral replication in cellular models of mice (in vivo) and human (ex vivo) airway epithelia cultures.…”

Section: Introductionmentioning

confidence: 99%

Thermodynamics and Kinetic Investigation of Reaction of Acriflavine with L-cysteine in Aqueous Medium

Nkole

Idris

2021

Chemistry Africa

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Graphic abstract The kinetic investigation of reaction of 3,6-diamino-10-methylacridin-10-ium chloride (acriflavine) with l-cysteine in aqueous acidic medium at maximum absorption = 460 nm, ionic strength (I) = 0.1 mol dm −3 and temperature (T) = 307 K has been carried out spectrophotometrically. Using a pseudo first order approach, the rate of the redox reaction resulted to first order with respect to the [acriflavine, (AF)] and [l-cysteine, (CSH)] and second order total. Stoichiometric determination confirms that a mole of the acriflavine is consumed by a mole of l-cysteine at a time for the attainment of product formation. The reaction followed a one-way acid independence path. The adjustment in ionic strength (NaCl) and solvent polarity (water/acetone mixture) of the reaction system showed no reasonable effect and there was a fairly decrease in the reaction rate, respectively. The reaction rate is also characterised by neither catalysis nor inhibition of added ions. The negative magnitude of entropy of activation, S ‡ , (− 151.39 ± 031 J mol −1 K −1 ) and positive value of enthalpy of activation, H ‡ , (+ 31.378 ± 030 kJ mol −1 ) suggest that the reaction proceeds via an associative pathway and reasonable energy are needed to lower the activation energy for a tangible products formation. Two acridine unit products polymerised afterward forming a dimer as a result of an intramolecular coupling. A determinable intermediate has been observed through a spectroscopic test and confirmed by Michaelis–Menten’s plot. Based on Taube’s inorganic electron transfer reaction, an inner-sphere mechanistic pathway is implicated with a stable intermediate complex formation as shown below;

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Acriflavine modification of nucleic acid formation, mutation induction and survival in ultraviolet light exposed bacteria

Cited by 32 publications

References 3 publications

Potent Antimalarial Activity of Acriflavine In Vitro and In Vivo

Potent Antimalarial Activity of Acriflavine In Vitro and In Vivo

Mechanism of Caffeine Enhancement of Mutations Induced by Sublethal Ultraviolet Dosages

Thermodynamics and Kinetic Investigation of Reaction of Acriflavine with L-cysteine in Aqueous Medium

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