No abstract

No abstract

The Aβ 42 amyloid aggregation and its stabilization by coordination metals like Zn II through chelation, are the major pathological causes behind the occurrence of Alzheimer's disease (AD). Natural compounds like curcumin and chrysamine G have depicted Aβ 42 aggregation inhibition, metal chelation and antioxidant properties. Likewise garlic derived diallyl disulfide (DADS) has shown metal chelation, acetylcholinesterase (AChE) inhibition and antioxidant properties. In the present study a library of thirty four unnatural symmetrical DADS derivatives with aliphatic, aryl and new heteroaryl spacer groups, has been designed on the basis of electron releasing/withdrawing substituents and N/O heteroatom. The library was screened using various theoretical tools for their molecular properties and bioactivity with different receptors, to filter eleven potentially active derivatives. Further, Molecular docking study with Aβ 42 (PDB ID: 1IYT) and Zn II -Aβ 16 (PDB ID: 1ZE9) displayed significant binding of heteroaryl DADS derivatives with highest binding energies and zinc binding ability. DFT calculations helped to predict their binding ability with free Zn II ion through disulfide linkage. MEP studies specified their reactive sites of binding. Finally, a synthetic protocol using less toxic reagents has been designed for their synthesis and an in vitro antioxidant activity has been evaluated.

Reaction of pyridinium phenacylids and their picolinium and isoquinolinium counterparts with substituted benzylideneacetophenones gave a wide variety of 2,4,6‐triaryl‐substituted pyridines which are expected to have some potential biological activities. Ammonium acetate in glacial acetic acid was used as the cyclization agent. The structures of resulting pyridines are supported by nmr and ir spectral data.

Interpolymer complexes of acrylamidehinyl alcohol graft copolymers (AAmNA) were prepared with two typical polyelectrolytes, e. g. poly(methacry1ic acid) (PMA) and poly(ethy1eneimine) (PEI). The equivalent blends of the same composition as the graft copolymer complexes were also prepared by mixing stoichiometric portions of binary homopolymer complexes. The stability constant (K), degree of linkage (8) and related thermodynamic parameters (e. g. standard free energy change AGO, standard enthalpy change AHo and standard entropy change ASo) were determined for each system by using Osada's method. The comparative study between graft copolymer complexes and equivalent blends indicated a considerable difference in these parameters. An interpretation of this discrepancy was sought in terms of copolymer effect, neighbouring group influence, and the nature of secondary binding forces upon interpolymer complexation.