Novel neuroprotective 5,6-dihydropyrido[2',1':2,3]imidazo[4,5-c]quinoline derivatives acting through cholinesterase inhibition and CB2 signaling modulation.

A novel group of 5,6-dihydropyrido [2',1':2,3]imidazo [4,5-c]quinolines was prepared via a microwave assisted one-pot telescopic approach. The synthetic sequence involves the formation of an amine precursor of imidazo [1,2-a]pyridine via condensation and reduction under microwave irradiation. Subsequently, the Pictet-Spengler cyclisation reaction occurs with ketones (cyclic or acyclic) to obtain substituted 5,6-dihydropyrido [2',1':2,3]imidazo [4,5-c]quinolines in excellent yields. The compounds were tested as neuroprotective agents. Observed protection of neuron-like cells, SH-SY5Y differentiated with ATRA, in Parkinson's and Huntington's disease models inspired further mechanistic studies of protective activity against damage induced by 1-methyl-4-phenylpyridinium (MPP+), a compound causing Parkinson's disease. The novel compounds exhibit similar or higher potency than ebselen, an established drug with antioxidant activity, in the cells against MPP + -induced total cellular superoxide production and cell death. However, they exhibit a significantly higher capacity to reduce mitochondrial superoxide and preserve mitochondrial membrane potential. We also observed marked differences between a selected derivative and ebselen in terms of normalizing MPP + -induced phosphorylation of Akt and ERK1/2. The cytoprotective activity was abrogated when signaling through cannabinoid receptor CB2 was blocked. The compounds also inhibit both acetylcholine and butyrylcholine esterases. Overall the data show that novel 5,6-dihydropyrido [2',1':2,3]imidazo [4,5-c]quinoline have a broad cytoprotective activity which is mediated by several mechanisms including mitoprotection.

Copper Catalyzed Synthesis of Heterocyclic Molecules via C-N and C-O Bond Formation under Microwaves: A Mini-Review.

Heterocyclic moieties play a significant role in the field of drug discovery. C-N and C-O bond formation reactions are the primary synthetic sequence for the generation of heterocyclic molecules. The generation of C-N and C-O bonds involves the use of mostly Pd or Cu catalysts although other transition metal catalyst's are also involved. However, in C-N and C-O bond formation reactions, several problems were faced such as catalytic systems containing costly ligands, lack of substrate scope, lots of waste generation, and high temperature conditions. So it is imperative to uncover new eco-friendly synthetic strategies. In view of enormous drawbacks, it is important to develop an alternate microwave-assisted synthesis of heterocycles via C-N and C-O bond formation, which provides a short reaction time, tolerance for functional groups, and less waste production. Numerous chemical reactions have been accelerated using microwave irradiation which provides a cleaner reaction profile, lower energy consumption, and higher yields. This review article highlights a comprehensive overview on the potential application of microwave assisted synthetic routes for the synthesis of diverse heterocycles via mechanistic pathways covering the year ranges from 2014 to 2023, along with possible biological interests.

Photophysical evaluation on the electronic properties of synthesized biologically significant pyrido fused imidazo[4,5-c]quinolines.

A single pot microwave assisted method was employed to synthesize a series of novel pyrido fused imidazo[4,5-c]quinolines. The electronic properties of these derivatives were investigated by following their photophysical behaviour under isolated and solvated conditions via computational and experimental approaches. The solvatochromic effect of these derivatives was investigated in the ground and excited singlet states by following the absorption and fluorescence emission and excitation spectra. Further the effect of general and specific solvent effects were also investigated by plotting Stokes shift against Lippert-Mataga, ET(30) and Kamlet-Taft polarity parameters respectively. The deviation from linearity in ET(30) plot indicates that formation of different species in polar protic solvents. The biological applications of these derivatives as potential drug candidates were evaluated by in silico computational methods followed by pharmacokinetic properties predictions. The ability of these derivatives to inhibit human casein kinase 2 (CK2) was evaluated. The structure activity relationships were correlated by evaluating the electronic properties through experimental photophysical investigations including solvatochromic effect and computational electronic structure calculations. Of the various derivatives, p-nitro phenyl substituted pyrido fused imidazo[4,5-c]quinoline exhibited good inhibitory activity against CK2 enzyme and hence could serve as a promising drug candidate.

Computationally approached inhibition potential of Tinospora cordifolia towards COVID-19 targets.

The recent emergence of novel coronavirus (SARS-CoV-2) has been a major threat to human society, as the challenge of finding suitable drug or vaccine is not met till date. With increasing morbidity and mortality, the need for novel drug candidates is under great demand. The investigations are progressing towards COVID-19 therapeutics. Among the various strategies employed, the use of repurposed drugs is competing along with novel drug inventions. Based on the therapeutic significance, the chemical constituents from the extract of Tinospora cordifolia belonging to various classes like alkaloids, lignans, steroids and terpenoids are investigated as potential drug candidates for COVID-19. The inhibition potential of the proposed compounds against viral spike protein and human receptor ACE2 were evaluated by computational molecular modeling (Auto dock), along with their ADME/T properties. Prior to docking, the initial geometry of the compounds were optimized by Density functional theory (DFT) method employing B3LYP hybrid functional and 6-311 + + G (d,p) basis set. The results of molecular docking and ADME/T studies have revealed 6 constituents as potential drug candidates that can inhibit the binding of SARS-CoV-2 spike protein with the human receptor ACE2 protein. The narrowed down list of constituents from Tinospora cordifolia paved way for further tuning their ability to inhibit COVID-19 by modifying the chemical structures and by employing computational geometry optimization and docking methods. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13337-021-00666-7.