Interrelation between the chemical structure and antioxidant properties of N-substituted amides of salicylic acid

Abstract

The kinetics of the initiated oxidation of a model lipid (methyl oleate has been investigated in the presence of a group of new "hybrid" structures, namely, N substituted amides of salicylic acid whose struc ture contains an amide residue conjugated with, or separated by a bridging fragment (three methylene groups) from, an N phenolic substituent. The compounds also differ in the degree of screening of the OH groups. The process was initiated by thermal decomposition of azobisisobutyronitrile at 60°C (initiation rate of w i = 4.2 × 10 -8 mol L -1 s -1 ) or by UV irradiation (λ = 313-365 nm, w i = 0.6 × 10 -8 mol L -1 s -1 ). The compounds examined exhibit antiradical activity owing to the presence of the phenolic hydroxyl groups. N substituted salicylamides efficiently inhibit the overall methyl oleate oxidation process and are comparable in activity with dibunolum and α tocopherol or are superior to them. The structures in which the residues of salicyla mide and sterically hindered phenol are separated by the bridging fragment are particularly efficient. The advantages of the salicylamides absorbing at 300-365 nm manifest themselves in UV initiated oxidation. The peroxidase activity of the N substituted salicyl acid derivatives is determined by the structure of the amide moiety. The compounds examined here are new, promising, effective antioxidants, whose particular structural fragments act via different mechanisms in oxidation.

Fast synthesis of amides from ethyl salicylate under microwave radiation in a solvent-free system

“…11 Fatty amide derivatives of SA also show a high affinity for stratum corneum and present safer topical application since they do not metabolize and enter into systemic circulation, accumulating in the uppermost layer of skin. 12,13 Lipophilic hydroxy acid derivatives of SA reduced the number of non-inammatory lesions of comedonal acne by up to 55.6% as compared to salicylic acid, which reduced it by 48.5%; 14 SA amides also present antioxidant activity and HIV-1 integrase inhibition, 15,16 same as observed with 3-keto SA chalcones, exhibiting HIV-1 integrase inhibition. 17 Therefore, SA and its analogues (amides, esters, fatty amides, and fatty acid) present a large number of biological activities and have been largely studied in academic, medicinal, and pharmaceutical areas.…”

Kinetics and Mechanism of Photoconversion of N-Substituted Amides of Salicylic Acid

“…As inert to the oxidation of the solvent, chlorobenzene purified by the simple distillation method was used. The temperature of the experiments is (60 AE 0.2) C [3,10]. From the kinetic curves, the period of induction (τ) was determined as a segment on the time scale, cut off by a perpendicular dropped from the point of intersection of the tangents.…”

“…It is known that salicylic acid and its derivatives are capable of absorbing UV rays in the range of 301-305 nm [3,8]. It can be assumed that the modified structures studied by us can also absorb UV rays in this range, which is dangerous for the development of skin cancer.…”

“…It has been established that all the derivatives of salicylic acid exhibit a high antiradical activity ( Table 1). Table 1 shows that the highest antiradical activity is found in natural antioxidant 6 (α-tocopherol), the efficacy of which is more than 400-460 times higher than that of compounds (1)(2)(3)(4). The absence of bulky substituents in structure 5 provides this compound the highest antiradical activity.…”

“…The mechanism of the destructive effect of UV rays is associated with the activation of free radical oxidation processes as a result of the formation of singlet oxygen [1]. Salicylic acid and its esters, the characteristic feature of which is maximum absorption in the range of 300 nm [1][2][3], are used to protect the skin from ultraviolet irradiation (methyl salicylate) and as promising photostabilizers of polymeric materials [4] and dyes [5]. Some N-substituted amide derivatives of salicylic acid serve as inhibitors of oxidation in the photo-irradiation of substrates and exceed in the efficiency of known synthetic and natural antioxidants [4].…”