Swayamsiddha Kar

Curcumin has antioxidant properties resulting from its radical scavenging ability and inhibition of inflammation‐associated factors. However, its lack of solubility, instability, and poor bioavailability are impediments to its therapeutic use. As potential alternatives, we synthesized and performed chemical analysis of thirty diarylidene‐N‐methyl‐4‐piperidone (DANMP), diheteroarylidene‐N‐methyl‐4‐piperidone (DHANMP), and spirobibenzopyran (SBP) derivatives, one of which was also characterized by single crystal X‐ray diffraction. All compounds were evaluated for antioxidant activity via 2,2‐Diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging assay and for drug‐like properties in silico. A subset of five compounds was investigated in terms of aqueous solubilities, which were significantly improved compared to that of curcumin. In vitro assessments of cellular and anti‐inflammatory effects were conducted via real time polymerase chain reaction (RT‐PCR) and Griess assays to evaluate the presence of inflammatory/activated (M1) markers and production of nitric oxide (NO) species, which are associated with inflammation. The five compounds reduced levels of markers and NO to extents similar to or better than curcumin in inflamed cells, and showed no adverse effects on cell viability. We show that these compounds possess anti‐inflammatory properties and may be used as curcumin‐substitutes with improved characteristics.

There is a significant need for new small molecule anti-inflammatory compounds. Curcumin, a small molecule natural product from the Turmeric (Curcuma longa) plant, has well-known anti-oxidant properties, resulting from its radical scavenging ability and inhibition of inflammation-associated factors. However, its lack of solubility, instability, and poor bioavailability and biodistribution characteristics are an impediment to its use. To circumvent these issues while retaining curcumin’s biological activity, we synthesized twenty-one diarylidene-N-methyl-4-piperidones (DANMPs), four diheteroarylidene-N-methyl-4-piperidones (DHANMPs), and five spirobibenzopyran (SBP) derivatives. All were screened in terms of anti-oxidant activity via a cell-free 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and for drug-like properties in silico. In the former, some compounds possessed improved radical scavenging behavior versus ascorbic acid, which was used as a benchmark. Conformity to simulated Lipinski’s parameters and Absorption, Distribution, Metabolism, and Excretion (ADME) studies indicated the DANMPs, DHANMPs, and SBPs to be potentially useful compounds. A subset of molecules was investigated in terms of their aqueous solubilities, which were significantly improved compared to that of curcumin. In vitro assessments of the cellular and anti-inflammatory effects of these compounds were conducted using RAW264.7 macrophages. RT-PCR and Griess assays were used to evaluate the presence of inflammatory/activated (M1) markers and production of nitric oxide (NO) species, which are associated with inflammation, respectively. While the compounds did not affect non-stimulated (naïve) macrophages, they did reduce levels of markers and NO to extents similar to or better than curcumin in inflamed cells. Our results indicate that these pharmacophores possess anti-inflammatory properties and can be used as curcumin-substitutes with improved characteristics. Further investigation into their mechanisms of action and potential use in the treatment of inflammatory diseases is merited.

A method for the microwave-assisted copper-mediated oxidative coupling reaction of different aldehydes and quinazolines/benzimidazoles has been developed for the synthesis of fused-polycyclic systems via new C–N bond formation. The current methodology involves the use of environmentally benign NH₄OAc as the amine source in the presence of 2-propanol as the solvent. This novel tandem reaction approach offers a rapid and straightforward access to complex fused quinazoline derivatives in an efficient manner.

This study establishes the diarylidenecyclohexanones as good anti-inflammatory pharmacophores with selective high potency against PGE₂and 5-LOX without toxicity towards healthy human cells.

This study is the first report on the anticancer activity of spirobibenzopyrans, an unexplored class of therapeutic agents. The synthesized spirobibenzopyrans were tested for anticancer activity across the NCI-60 cell-line panel. The in vitro and in silico results of the spirobibenzopyrans showed tremendous drug likeness scores as potential anticancer agents.