Polyamines and α-Carbonic Anhydrases

Abstract

Natural products represent a straightforward source for molecular structures bearing a vast array of chemical features and potentially useful for biomedical purposes. Recent examples of this type include the discovery of the coumarins and the polyamine natural products as atypical chemotypes for the inhibition of the metalloenzymes carbonic anhydrases (CAs; EC 4.2.2.1). CA enzymes are established pharmacological targets for important pathologies, which, among others, include glaucoma, hypoxic tumors, and central nervous system (CNS)-affecting diseases. Moreover, they are expressed in many bacteria, fungi and helminths which are the etiological agents of the majority of infectious diseases. In this context, natural products represent the ideal source of new and selective druggable CA modulators for biomedical purposes. Herein we report the state of the art on polyamines of natural origin as well as of synthetic derivatives as inhibitors of human CAs.

Synthesis, CYP 450 evaluation, and docking simulation of novel 4‐aminopyridine and coumarin derivatives

“…Coumarins, both synthetic and plant‐derived natural products, are known for their biological and pharmacological properties, such as anti‐inflammatory, anticancer, antioxidant, and neuroprotective properties . A large number of coumarin derivatives have been established as valuable potential resources for the prevention and therapy of CNS diseases in vitro and in vivo and as K + channel blockers, such as osthole, coumarsabin, 4‐phenoxybutoxy‐substituted coumarins or furochromones and 3‐ or 4‐pyridyl coumarins . 3‐(4‐Aminophenyl)‐2 H ‐chromen‐2‐one (CMC), 3‐(4‐(dimethylamino)phenyl)‐6‐(2‐fluoroethoxy)‐2 H ‐chromen‐2‐one (FCP), and 5,7‐disubstituted coumarins are known to exhibit promising myelin‐binding properties in MS treatment, among 36 studied coumarin derivatives.…”

Research Progress and Potential Applications of Spermidine in Ocular Diseases

“…In vivo, putrescine must be converted to spermidine to overcome MAG inhibition, while the application of spermidine alone was enough to promote optic nerve regeneration in a dose-dependent manner, as mentioned above [ 20 ]. In addition, spermidine can inhibit the metalloenzyme carbonic anhydrase, an established pharmacological target for glaucoma, by anchoring to the zinc-coordinated water molecule [ 113 , 114 ]. Among glaucoma patients, inhibiting carbonic anhydrase can effectively alleviate ocular hypertension by reducing the rate of bicarbonate formation, thus decreasing the secretion of the aqueous humor [ 115 ] and exhibiting the potential of spermidine in treating glaucoma.…”

Carbonic anhydrase inhibitors based on sorafenib scaffold: Design, synthesis, crystallographic investigation and effects on primary breast cancer cells

“…In addition new moieties include molecules able to interact to the zinc coordinated water/hydroxide ion (i.e. phenols [12][13][14][15][16], carboxylic acids [16,17], polyamines [18,19], thiooxycoumarins [20,21] and the sulfamic acid group from hydrolysis of sulfocoumarins [22][23][24][25][26][27][28]), compounds occluding the entrance of the CA active site (cinnamic acid derivatives from in situ hydrolyzed coumarins [20,[29][30][31][32]) and out of the site CAIs such as the 2-(benzylsulfonyl)-benzoic acid [33]. Although many CAI chemical moieties were reported, the selectivity in targeting specific enzymatic isoforms was not granted.…”