Series Of Salicylic Acid Derivatives Research Articles

A New Series of Salicylic Acid Derivatives as Non-saccharide α-Glucosidase Inhibitors and Antioxidants.

In this study, a series of salicylic acid derivatives were designed and synthesized as novel non-saccharide α-glucosidase inhibitors. Biological evaluation indicated that when compared to acarbose, compounds T9, T10, and T32 exhibited a higher potency of α-glucosidase inhibitory activity with IC50 values of 0.15 ± 0.01, 0.086 ± 0.01 and 0.32 ± 0.02 mM, respectively. Evaluation of the inhibition kinetics indicated that T9, T10, T32, and acarbose interacted with α-glucosidase in a mixed non-competitive inhibitory manner. Moreover, T9, T10, and T32 statically quenched the fluorescence of α-glucosidase by formation of an inhibitor-α-glucosidase complex. The docking results showed that hydrogen bonds were generated between the test compounds and α-glucosidase. The antioxidant study revealed that compound T10 exhibited a higher antioxidant activity via scavenging 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH), thereby inhibiting lipid peroxidation and the total reduction capacity. In brief, the salicylic acid derivatives identified in this study were promising candidates for development as novel non-saccharide α-glucosidase inhibitors.

Synthesis and biological evaluation of salicylic acid conjugated isoxazoline analogues on immune cell proliferation and angiogenesis

Mitogenicity is the ability of the natural or synthetic compounds to induce cell division or proliferation. A series of salicylic acid derivatives containing isoxazoline moiety (8a-j) were synthesized and their immunopharmacological activities targeting lymphocyte proliferation and angiogenesis were evaluated. The compounds 8a-j mitogenicity were investigated on immunological cells that include human peripheral blood lymphocytes and murine splenocytes in-vitro. The results implicate that among the series of 8a-j, compound 8e showed a potent proliferative response on both human and murine lymphocytes. The proliferative index of the compound 8e was comparable to the reference mitogen Con A and mitogenecity is due to increased secretion IL-2. In -vivo CAM and rat corneal angiogenesis assays were performed to assess the compound's effect on endothelial cell migration and proliferation which inferred that 8e also induces the proliferation of endothelial cells. The study reports the synthetic immunostimulatory and pro-angiogenic activity of novel mitogen 8e which could be translated into new drug in future.

The antioxidant properties of salicylate derivatives: A possible new mechanism of anti-inflammatory activity

The synthesis and antioxidant evaluation by DPPH scavenging of a series of salicylic acid derivatives is described. Gentisic acid and its ester, amide, and amino analogs possess more radical scavenging capacity than salicylic acid and other salicylate derivatives. This property can possibly provide an additional pathway for anti-inflammatory activity through either single electron or hydrogen atom transfer, leading to a new strategy for the design of anti-inflammatory agents.

A computational acumen into the relative applicability of geometrical and quantum chemical criteria in assessing intramolecular hydrogen bonding (IMHB) interaction: 5-Halosalicylic acids as representative examples

Density functional theory (DFT) based computational study has been performed to characterize intramolecular hydrogen bonding (IMHB) interaction in a series of salicylic acid derivatives having different halogen substitution at the 5-position on the benzene ring. The molecular systems studied are salicylic acid (SA), 5-fluorosalicylic acid (5FSA), 5-chlorosalicylic acid (5ClSA) and 5-bromosalicylic acid (5BrSA). Particular emphasis has been given on the analysis of IMHB interaction by the calculation of electron density ρ(r) and Laplacian ∇2ρ(r) at the bond critical point using Atoms-In-Molecule (AIM) theory. Topological features and energy densities based on ρ(r) through the perturbation of the IMHB distances suggest that at equilibrium geometry the IMHB interaction develops certain characteristics typical of a covalent interaction. Concomitantly, the role of charge transfer interaction in the IMHB has been critically addressed under the provision of Natural Bond Orbital (NBO) analysis. The formation of Resonance Assisted Hydrogen Bond (RAHB) in the studied molecular systems is also delineated from quantum chemical calculations. The interplay between aromaticity and RAHB is discussed in this context using both geometrical and magnetic criteria as the aromaticity descriptors. The optimized geometry features, analysis of the molecular electrostatic potential map have also been found to produce a consensus view in relation with the formation of RAHB in the studied systems. The lack of a specific pattern of IMHB energy in the studied molecules with the electronegativity of the substituent has also been attempted to address critically. Another major aspect of the present study is the argument about the superiority of quantum chemical criteria over geometrical criteria for the assessment of IMHB interaction in the studied compounds.

Geometrical criteria versus quantum chemical criteria for assessment of intramolecular hydrogen bond (IMHB) interaction: A computational comparison into the effect of chlorine substitution on IMHB of salicylic acid in its lowest energy ground state conformer

Density functional theory based computational study has been performed to characterize intramolecular hydrogen bonding (IMHB) interaction in a series of salicylic acid derivatives varying in chlorine substitution on the benzene ring. The molecular systems studied are salicylic acid, 5-chlorosalicylic acid, 3,5-dichlorosalicylic acid and 3,5,6-tricholorosalicylic acid. Major emphasis is rendered on the analysis of IMHB interaction by calculation of electron density ρ(r) and Laplacian ∇2ρ(r) at the bond critical point using atoms-in-molecule theory. Topological features, energy densities based on ρ(r) through perturbing the intramolecular H-bond distances suggest that at equilibrium geometry the IMHB interaction develops certain characteristics typical of covalent interaction. The interplay between aromaticity and resonance-assisted hydrogen bonding (RAHB) is discussed using both geometrical and magnetic criteria as the descriptors of aromaticity. The optimized geometry features, molecular electrostatic potential map analysis are also found to produce a consensus view in relation with the formation of RAHB in these systems.

A Disalicylic Acid‐Furanyl Derivative Inhibits Ephrin Binding to a Subset of Eph Receptors

Eph receptor tyrosine kinases and ephrin ligands control many physiological and pathological processes, and molecules interfering with their interaction are useful probes to elucidate their complex biological functions. Moreover, targeting Eph receptors might enable new strategies to inhibit cancer progression and pathological angiogenesis as well as promote nerve regeneration. Because our previous work suggested the importance of the salicylic acid group in antagonistic small molecules targeting Eph receptors, we screened a series of salicylic acid derivatives to identify novel Eph receptor antagonists. This identified a disalicylic acid-furanyl derivative that inhibits ephrin-A5 binding to EphA4 with an IC(50) of 3 μm in ELISAs. This compound, which appears to bind to the ephrin-binding pocket of EphA4, also targets several other Eph receptors. Furthermore, it inhibits EphA2 and EphA4 tyrosine phosphorylation in cells stimulated with ephrin while not affecting phosphorylation of EphB2, which is not a target receptor. In endothelial cells, the disalicylic acid-furanyl derivative inhibits EphA2 phosphorylation in response to TNFα and capillary-like tube formation on Matrigel, two effects that depend on EphA2 interaction with endogenous ephrin-A1. These findings suggest that salicylic acid derivatives could be used as starting points to design new small molecule antagonists of Eph receptors.

A Versatile and Practical Synthesis toward the Development of Novel HIV‐1 Integrase Inhibitors

As a continuation of our previous work, which resulted in the identification of a new hit compound as an HIV-1 integrase inhibitor, three novel series of salicylic acid derivatives were synthesized using three versatile and practical synthetic strategies and were assayed for their capacity to inhibit the catalytic activity of HIV-1 integrase. Biological evaluations revealed that some of the synthesized compounds possess good inhibitory potency in enzymatic assays and are able to inhibit viral replication in MT-4 cells at low micromolar concentrations. Finally, docking studies were conducted to analyze the binding mode of the synthesized compounds within the DNA binding site of integrase in order to refine their structure-activity relationships.

In vitro inhibition of salicylic acid derivatives on human cytosolic carbonic anhydrase isozymes I and II

The inhibition of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes, hCA I and II, with a series of salicylic acid derivatives was investigated by using the esterase method with 4-nitrophenyl acetate as substrate. IC 50 values for sulfasalazine, diflunisal, 5-chlorosalicylic acid, dinitrosalicylic acid, 4-aminosalicylic acid, 4-sulfosalicylic acid, 5-sulfosalicylic acid, salicylic acid, acetylsalicylic acid (aspirin) and 3-metylsalicylic acid were of 3.04 μM, 3.38 μM, 4.07 μM, 7.64 μM, 0.13 mM, 0.29 mM, 0.42 mM, 0.56 mM, 2.71 mM and 3.07 mM for hCA I and of 4.49 μM, 2.70 μM, 0.72 μM, 2.80 μM, 0.75 mM, 0.72 mM, 0.29 mM, 0.68 mM, 1.16 mM and 4.70 mM for hCA II, respectively. Lineweaver–Burk plots were also used for the determination of the inhibition mechanism of these substituted phenols, most of which were noncompetitive inhibitors with this substrate. Some salicylic acid derivatives investigated here showed effective hCA I and II inhibitory activity, and might be used as leads for generating enzyme inhibitors eventually targeting other isoforms which have not been assayed yet for their interactions with such agents.

Stability of Metal Complexes of Nuclear-Substituted Salicylic Acids: Correlation with Biological Effects

Stability constants are reported for the chelation of ferric and aluminum ions by a series of salicylic acid derivatives having amino, alkyl, chloro, and nitro groups in the ring. The sequence of complex stabilities found is in agreement with current organic theory and shows a parallelism with the ionization constants. Three of the biological effects known for salicylates, antibacterial, analgesic-antipyretic, and fungicidal, can be related to the magnitude of complex stability or ionization constant.

Biochemical studies of salicylic acid and a series of its derivatives

A series of salicylic acid derivatives was studied for duration of blood salicyl levels in the rabbit. The series comprised salicylic acid, sodium salicylate, acetylsalicylic acid, a solubilized acetylsalicylic acid, nicotinyl salicylate, salicyoyl-beta-alanide, acetylsaligenin, the salicylic acid ester of succinic acid, acetylsalicylaldehyde diacetate, the amide of o-aminobenzoic and salicylic acids, and saligenin. The effective compounds were studied in combination and singly. Of this series, the most effective single compound was found to be nicotinyl salicylate and the most effective combination was one of nicotinyl salicylate and saligenin.