Nevskaya_2021_Molecules_26_

Reference

Title : Homobivalent Lamellarin-Like Schiff Bases: In Vitro Evaluation of Their Cancer Cell Cytotoxicity and Multitargeting Anti-Alzheimer's Disease Potential - Nevskaya_2021_Molecules_26_
Author(s) : Nevskaya AA , Anikina LV , Purgatorio R , Catto M , Nicolotti O , de Candia M , Pisani L , Borisova TN , Miftyakhova AR , Varlamov AV , Nevskaya EY , Borisov RS , Voskressensky LG , Altomare CD
Ref : Molecules , 26 : , 2021
Abstract :

Marine alkaloids belonging to the lamellarins family, which incorporate a 5,6-dihydro-1-phenylpyrrolo[2,1-a]isoquinoline (DHPPIQ) moiety, possess various biological activities, spanning from antiviral and antibiotic activities to cytotoxicity against tumor cells and the reversal of multidrug resistance. Expanding a series of previously reported imino adducts of DHPPIQ 2-carbaldehyde, novel aliphatic and aromatic Schiff bases were synthesized and evaluated herein for their cytotoxicity in five diverse tumor cell lines. Most of the newly synthesized compounds were found noncytotoxic in the low micromolar range (<30 microM). Based on a Multi-fingerprint Similarity Search aLgorithm (MuSSeL), mainly conceived for making protein drug target prediction, some DHPPIQ derivatives, especially bis-DHPPIQ Schiff bases linked by a phenylene bridge, were prioritized as potential hits addressing Alzheimer's disease-related target proteins, such as cholinesterases (ChEs) and monoamine oxidases (MAOs). In agreement with MuSSeL predictions, homobivalent para-phenylene DHPPIQ Schiff base 14 exhibited a noncompetitive/mixed inhibition of human acetylcholinesterase (AChE) with K(i) in the low micromolar range (4.69 microM). Interestingly, besides a certain inhibition of MAO A (50% inhibition of the cell population growth (IC(50)) = 12 microM), the bis-DHPPIQ 14 showed a good inhibitory activity on self-induced beta-amyloid (Abeta)(1-40) aggregation (IC(50) = 13 microM), which resulted 3.5-fold stronger than the respective mono-DHPPIQ Schiff base 9.

PubMedSearch : Nevskaya_2021_Molecules_26_
PubMedID: 33445600

Related information

Citations formats

Nevskaya AA, Anikina LV, Purgatorio R, Catto M, Nicolotti O, de Candia M, Pisani L, Borisova TN, Miftyakhova AR, Varlamov AV, Nevskaya EY, Borisov RS, Voskressensky LG, Altomare CD (2021)
Homobivalent Lamellarin-Like Schiff Bases: In Vitro Evaluation of Their Cancer Cell Cytotoxicity and Multitargeting Anti-Alzheimer's Disease Potential
Molecules 26 :

Nevskaya AA, Anikina LV, Purgatorio R, Catto M, Nicolotti O, de Candia M, Pisani L, Borisova TN, Miftyakhova AR, Varlamov AV, Nevskaya EY, Borisov RS, Voskressensky LG, Altomare CD (2021)
Molecules 26 :