90-24-4Relevant articles and documents
Total Synthesis and Cytotoxic Activity of 6,8-Dimethoxy-1,3-dimethylisoquinoline Isolated from Ancistrocladus tectorius: A 6π-Azaelectrocyclization Approach
Cortés, Iván,Borini Etichetti, Carla M.,Girardini, Javier E.,Kaufman, Teodoro S.,Bracca, Andrea B. J.
, p. 433 - 440 (2019)
A facile and convenient approach toward the total synthesis of 1,3-dimethyl-6,8-dimethoxyisoquinoline from phloroacetophenone is reported. The sequence entailed the selective 2,4-di-O-methylation and further triflation of the resulting phenolic product. This was followed by a Stille-type allylation, an allyl-to-propenyl isomerization, and the methoximation of the carbonyl moiety. A final microwave-assisted 6π-azaelectrocyclization completed the sequence. Functionalized derivatives on C-1 were also prepared. The heterocycles exhibited cytotoxic activity.
Dual inhibitors of Interleukin-6 and acetylcholinesterase for treatment of Alzheimer's disease: Design, docking, synthesis and biological evaluation
Bansal, Yogita,Kaur, Sukhvir
, (2021/11/13)
Multitarget compounds intercept two or more functionally complementary pathways simultaneously, and are therefore considered to have potential in effectively treating complex multifactorial diseases like Alzheimer's disease (AD). In the present study, novel molecules are designed by coupling a chromone and a N,N-disubstituted carbamoyl amine as pharmacophore for interleukin-6 (IL-6) and acetylcholinesterase (AChE) inhibition, respectively. Four series (Y1–Y4) of 40 compounds are designed by using alkyl linkers of different lengths (1–4 carbon atoms) for the coupling of the two selected pharmacophore. Docking of all designed compounds in AChE leads to the identification of twelve best fit compounds (Docking score >8.3). The data suggests that a 1- or 2-carbon atom linker is the most conducive to orient the pharmacophore for optimum binding with AChE active site. The predicted ADME properties of the 12 selected compounds suggest that these can cross the blood brain barrier (BBB) with good oral bioavailability. These compounds are synthesised and evaluated for anti-AChE activity. Five compounds, showing >45% inhibition of AChE, are further evaluated for IL-6 inhibitory activity. Compound Y1f is found to be the most potent inhibitor of both AChE and IL-6 (IC50 0.7 and 0.8 ?μM, respectively). It suggests that a chromone moiety connected to a piperidine ring through a 1-carbon atom linker may provide a useful template to medical chemists for the development of new chemical entities effective against AD.
The first synthesis of podocarflavone A and its analogs and evaluation of their antimycobacterial potential against Mycobacterium tuberculosis with the support of virtual screening
Puranik, Ninad V.,Swami, Sagar,Misar, Ashwini V.,Mamgain, Ritu,Gulawani, Swapnaja S.,Sarkar, Dhiman,Srivastava, Pratibha,Srivastava, Pratibha
supporting information, (2021/03/15)
The first synthetic route developed for Podocarflavone A reported from Podocarpus macrophyllus and its analogs in 7 steps. Computational analysis for binding with the pantothenate kinase (3AVO) of Mycobacterium tuberculosis showed their docking score (ds) in the range of ?8.9 to ?9.3 Kcal/mol. MD simulations delineated the stability of the protein-ligand complexes in the TIP3P model. MMGBSA and MMPBSA values of 8d were ?42.46 Kcal/mol and ?14.58 Kcal/mol, respectively. Further in-vitro antitubercular screening of compounds 8a, 8d, and 8e against M. tuberculosis H37Ra using XRMA protocol exhibited promising antimycobacterial activity with IC50 values 21.82μg/mL, 15.55 μg/mL, and 16.56 μg/mL, respectively. Compounds 8a, 8d, and 8e showed antibacterial activity with IC50 values 41.56 μg/mL, 24.72 μg/mL, and 72.45 μg/mL respectively against the Staphylococcus aureus. 8a and 8d showed inhibition with IC50 values 39.6 μg/mL and 27.64 μg/mL, respectively, against Bacillus subtilis. The present study could help in the further development of lead molecules against tuberculosis.
