Evaluation of O-alkyl and aryl sulfonyl aromatic and heteroaromatic amidoximes as novel potent DNA photo-cleavers

Abstract

Several stable O-alkyl and aryl sulfonyl conjugated p-nitro-Ph and o-, m-, p-pyridine N'-hydroxy imidamides, were subjected to UV irradiation at 312 nm with supercoiled circular plasmid DNA pBluescript KS II. The generated amidinyl and sulfonyloxyl radicals led to effective DNA photo-cleavage. Both alkyl and aryl sulfonyl derivatives were active and the order p-pyridine > p-nitro-Ph > o-pyridine > m-pyridine was schematized for the N'-hydroxy imidamides moiety. Calf thymus-DNA affinity studies which comprised UV interactions, viscosity experiments and competitive studies with ethidium bromide showed good to excellent affinity of the compounds. These properties revealed sulfonyl amidoximes as novel effective DNA-photo-cleavers and may serve in the discovery of new leads for "on demand" biotechnological and medical applications.

Alkyl and aryl sulfonyl p-pyridine ethanone oximes are efficient DNA photo-cleavage agents

“…Taking τ o = 23 ns as the fluorescence lifetime of EB-DNA system [33], the quenching constants of the compounds as calculated ; the values of the k q constants are significantly higher than 10 10 M −1 s −1 suggesting, thus, the quenching via a static mechanism [34]. A current study from our group, concerning the photo-cleavage of sulfonyl amidoximes [35], show results which are in general agreement with the observations of the present. However, SKs presented herein show better activity.…”

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

“…O-Acyl amidoximes, ketoximes and aldoximes (I, II and III, respectively, Figure 1) are also recognized as DNA "photocleavage" agents owing their action to the homolysis of their vulnerable N-O bond, at 312 nm [9,[39][40][41][42][43] or 365 nm [44,45] yielding photogenerated carbonyloxyl radicals (CRs), which are able to cause oxidative DNA damage. We have recently reported the DNA photocleavage from sulfonylamidoximes and ethanone oximes (IV and V, Figure 1), which were found to attack DNA via sulfonyloxyl radicals (SRs) [10,11]. All the above radical species exhibit photoreactivity towards DNA.…”

“…Small organic molecules able to bind DNA provide promises for anticancer activity due to alteration of the structure and function of the genetic material. Amongst a plethora of such binders [1][2][3][4][5][6][7][8], various oxime derivatives were found to show affinity towards DNA [9][10][11][12], whereas others were found to cleave DNA as metal-free artificial nucleases [13,14].…”

“…Based on our interest in the chemistry and biology of the oxime functionality [54][55][56][57], as well as in their DNA photolytic interaction upon UV irradiation [9][10][11]43] we have decided to investigate the behaviour of carefully designed O-carbamoyl derivatives of p-pyridine amidoxime, ethanone oxime and aldoxime (VI, VII, VIII, R 1 = p-pyridyl, Figure 1) as DNA photosensitizers. Based on our previous ex-Scheme 1: Synthesis of O-carbamoyl amidoximes (8)(9)(10)(11)(12)(13), ethanone oximes (15)(16)(17)(18)(19)(20) and aldoximes (22)(23)(24)(25)(26)(27). Oxime 1 or 14 or 21, Et 3 N (1.1 equiv), R-NCO (1.1-1.8 equiv), dry chloroform or tetrahydrofuran, Ar, 0 °C → rt or reflux, 19-97%.…”

“…perimental results with o-, m-and p-pyridine oximes as carriers of the carboxylic [9] and sulfonic [11] ester conjugates, we proclaimed p-substituted pyridine ring as the most appropriate oxime supporting scaffold for experimenting with our novel carbamate esters, because this ring exhibited a better profile compared to the other pyridine analogues [9,11]. In order to provide a structure-activity relationship study, a series of O-carbamoyl conjugates consisted of benzyl as well as phenyl groups, bearing electron donating or withdrawing substituents, were synthesized and evaluated.…”