Malabaricone C, a constituent of spice Myristica malabarica, exhibits anti-inflammatory effects via modulation of cellular redox.

The present study primarily focuses on the efficacy of Malabaricone C (Mal C) as an anti-inflammatory agent. Mal C inhibited mitogen-induced T-cell proliferation and cytokine secretion. Mal C significantly reduced cellular thiols in lymphocytes. N-acetyl cysteine (NAC) restored cellular thiol levels and abrogated Mal C-mediated inhibition of T-cell proliferation and cytokine secretion. Physical interaction between Mal C and NAC was evinced from HPLC and spectral analysis. Mal C treatment significantly inhibited concanavalin A-induced phosphorylation of ERK/JNK and DNA binding of NF-κB. Administration of Mal C to mice suppressed T-cell proliferation and effector functions ex vivo. Mal C treatment did not alter the homeostatic proliferation of T-cells in vivo but completely abrogated acute graft-versus-host disease (GvHD)-associated morbidity and mortality. Our studies indicate probable use of Mal C for prophylaxis and treatment of immunological disorders caused due to hyper-activation of T-cells.

Synthesis of Dihydrobenzofuro[3,2-b]chromenes as Potential 3CLpro Inhibitors of SARS-CoV-2: A Molecular Docking and Molecular Dynamics Study.

The recent emergence of pandemic of coronavirus (COVID-19) caused by SARS-CoV-2 has raised significant global health concerns. More importantly, there is no specific therapeutics currently available to combat against this deadly infection. The enzyme 3-chymotrypsin-like cysteine protease (3CLpro) is known to be essential for viral life cycle as it controls the coronavirus replication. 3CLpro could be a potential drug target as established before in the case of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). In the current study, we wanted to explore the potential of fused flavonoids as 3CLpro inhibitors. Fused flavonoids (5a,10a-dihydro-11H-benzofuro[3,2-b]chromene) are unexplored for their potential bioactivities due to their low natural occurrences. Their synthetic congeners are also rare due to unavailability of general synthetic methodology. Here we designed a simple strategy to synthesize 5a,10a-dihydro-11H-benzofuro[3,2-b]chromene skeleton and it's four novel derivatives. Our structural bioinformatics study clearly shows excellent potential of the synthesized compounds in comparison to experimentally validated inhibitor N3. Moreover, in-silico ADMET study displays excellent druggability and extremely low level of toxicity of the synthesized molecules. Further, for better understanding, the molecular dynamic approach was implemented to study the change in dynamicity after the compounds bind to the protein. A detailed investigation through clustering analysis and distance calculation gave us sound comprehensive data about their molecular interaction. In summary, we anticipate that the currently synthesized molecules could not only be a potential set of inhibitors against 3CLpro but also the insights acquired from the current study would be instrumental in further developing novel natural flavonoid based anti-COVID therapeutic spectrums.

Azobenzene Isomerization-Induced Photomodulation of Electronic Properties of N-Heterocyclic Carbenes.

Azobenzene-based protonated N-heterocyclic carbenes (NHCs), N,N'-bis(azobenzene)imidazolium chlorides (IAz-X⋅HCl; X=OMe, Br, H) were successfully synthesized and switching abilities of the attached azobenzene units along with the concomitant photoinduced generation of geometric isomers were studied. Upon irradiation with 365 nm UV light, a p-methoxy-azobenzene derivative get transformed from all-trans isomer to nearly all-cis isomer at the photostationary state. The extent of photomodulation of electronic properties in the NHC ring of the p-methoxy-azobenzene derivative is determined through the Tolman Electronic Parameter (TEP). Iridium complex, [(IAz-OMe)IrCl(CO)2 ] was synthesized and infrared spectra were recorded in dichloromethane solution as film in NaCl crystals and by drop-casting in an ATR crystal. Comparison in averaged carbonyl stretching frequency between all-trans isomer ( ν ˜ t t av ) and all-cis isomer ( ν ˜ c c a v ) indicates a significant decrement of Δtt-cc ν ˜ av =2.7 cm-1 (film) and 3.8 cm-1 (ATR). Therefore, moderate to excellent enhancement of electron density (Δtt-cc TEP=2.3 cm-1 [film] and 3.2 cm-1 [ATR]) at the C-2 position of the NHC is achieved through trans→cis isomerization of the remotely placed azobenzene units. This fine phototuning of electron-donating ability at the catalytic center would pave the way to control NHC/NHC-metal catalyzed organic transformations through external stimuli.

Total Syntheses of Malabaricones B and C via a Cross-Metathesis Strategy.

The malabaricones A-D belong to the class of diarylnonanoids isolated from the Myristicaceae family of plants. Although malabaricone C displayed various interesting biological activities, its isolation remains tedious due to its close chemical similarity to malabaricones A, B, and D. Therefore, development of an efficient synthesis route has become essential to cater to the need of large amounts of malabaricone C for its pharmacological profiling. So far there is only one report of the synthesis of malabaricone C through a lengthy sequence of reactions. We have developed an efficient and short route for the syntheses of malabaricones B and C, which will also provide a convenient access to all other members of the malabaricone family. Synthesis of an important building block, ω-aryl heptyl bromide, employed in the synthesis was realized by adopting a cross-metathesis reaction as the key step.

Recognition of steric factor in external association of xanthenocrown-5 and bis-napthalenocrown-6 with bis(benzimidazolium)propane borontetrafluoride.

This is the first report of charge transfer band for crown-axel H-bonding interaction in acetonitrile medium. Monte Carlo simulation established external association of small cavity crown with BBIM-propane dication axels. Resonance energy, binding constant and ratiometric detection of association of xanthenocrown-5 (1) and bis-napthalenocrown-6 (2) with bis-(benzimidazolium)propane borontetrafluoride (3a-3d) in acetonitrile determined the effect of steric factor towards association.

PyC60-naphthacrown system: a new supramolecular recognition element.

Fulleropyrrolidine (PyC60) and a binaphthyl bridged crown ether macrocyclic receptor (1) undergoes spontaneous self-assembly phenomenon in solution to generate a new supramolecular recognition element having binding constant value of ∼5.83×10(4)dm(3)mol(-1). Lifetime measurement reveals a static quenching mechanism behind the deactivation of photoexcited state of 1 in presence of PyC60. The results obtained from this work would definitely reinforce bridged cyclic crown ether as one of the most suitable fragments for the molecular recognition of various macrocyclic receptor(s) in near future.

Absorption spectrophotometric, NMR and theoretical investigations on ground state non-covalent interaction of C60 and C70 with a designed trihomocalix[6]arene in solution.

The present paper reports the spectroscopic investigations on non-covalent interaction of fullerenes C(60) and C(70) with a designed trihomocalix[6]arene (2) in toluene. UV-vis studies reveal appreciable ground state interaction between fullerenes and 2. Jobs method of continuous variation establishes 1:1 stoichiometry for fullerene-2 complexes. Binding constant (K) data reveals that 2 binds C(70) more strongly compared to C(60), i.e. K(C60-2)-47,540 dm(3)mol(-1) and K(C70-2)-86,360 dm(3)mol(-1). Proton NMR studies provide very good support in favor of strong binding between C(70) and 2. Estimation of solvent reorganization energy (R(S)) evokes that C(70)-2 complex is stabilized more compared to C(60)-2 complex as R(S(C60-2))- -1.162 eV and R(S(C70-2))- -1.244eV. Semiempirical calculations at third parametric level of theory in vacuo evoke the single projection structures of the fullerene-2 complexes and interpret the stability difference between C(60) and C(70) complexes of 2 in terms of enthalpies of formation values.