Visible-light promoted catalyst-free (VLCF) multi-component synthesis of spiro indolo-quinazolinone-pyrrolo[3,4-a]pyrrolizine hybrids: evaluation of in vitro anticancer activity, molecular docking, MD simulation and DFT studies.

A new and highly efficient visible-light-promoted catalyst free (VLCF) strategy for neat and clean synthesis of spiro indolo-quinazolinone-pyrrolo[3,4-a]pyrrolizine hybrids (6a-d) has been introduced. We have performed visible-light triggered 1,3-Dipolar cycloaddition reaction of maleimide (5a-d) with azomethine ylide generated in situ derived from tryptanthrin (3) and L-proline (4) to obtain desired products (6a-d) in good to excellent yield. Authentication and characterization of product was done using various spectroscopic techniques such as IR, 1H NMR, 13C NMR, Mass spectrometry and single crystal XRD analysis. To explain the reaction spontaneity, product stability, reactivity as well as possible mode of the interaction a quantum chemical investigation was performed and depicted through DFT studies. The synthesized compound 6a was also evaluated for anti-proliferative activity against a panel of five cancer cell lines (MCF-7, MDA-MB-231, HeLa, PC-3 and Ishikawa) and normal human embryonic kidney (HEK-293) cell line by using MTT assay. Compound 6a showed very good in vitro anti-proliferative activity (IC50  = 6.58-17.98 µM) against four cancer cell lines and no cytotoxicity against normal HEK-293. In order to evaluate the anticancer potential of compounds 6a-d, molecular docking was performed against wild type and mutant EGFR. The results suggest that all the compounds occupied the active site of both enzymes, with a strong binding energy (-10.2 to -11.5 kcal/mol). These results have been confirmed by molecular dynamics simulation by evaluating root mean square deviation (RMSD) and root mean square fluctuation (RMSF), along with principal component analysis (PCA).Communicated by Ramaswamy H. Sarma.

Visible Light-Promoted Green and Sustainable Approach for One-Pot Synthesis of 4,4'-(Arylmethylene)bis(1H-pyrazol-5-ols), In Vitro Anticancer Activity, and Molecular Docking with Covid-19 Mpro.

A visible light-promoted, efficient, green, and sustainable strategy has been adopted to unlatch a new pathway toward the synthesis of a library of medicinally important 4,4'-(arylmethylene)bis(1H-pyrazol-5-ols) moieties using substituted aromatic aldehydes and sterically hindered 3-methyl-1-phenyl-2-pyrazoline-5-one in excellent yield. This reaction shows high functional group tolerance and provides a cost-effective and catalyst-free protocol for the quick synthesis of biologically active compounds from readily available substrates. Synthesized compounds were characterized by spectroscopic techniques such as IR, 1HNMR, 13CNMR, and single-crystal XRD analysis. All the synthesized compounds were evaluated for their antiproliferative activities against a panel of five different human cancer cell lines and compared with Tamoxifen using MTT assay. Compound 3m exhibited maximum antiproliferative activity and was found to be more active as compared to Tamoxifen against both the MCF-7 and MDA-MB-231 cell lines with an IC50 of 5.45 and 9.47 µM, respectively. A molecular docking study with respect to COVID-19 main protease (Mpro) (PDB ID: 6LU7) has also been carried out which shows comparatively high binding affinity of compounds 3f and 3g (-8.3 and -8.8 Kcal/mole, respectively) than few reported drugs such as ritonavir, remdesivir, ribacvirin, favipiravir, hydroxychloroquine, chloroquine, and olsaltamivir. Hence, it reveals the possibility of these compounds to be used as effective COVID-19 inhibitors.

A modular approach for molecular recognition by zinc dipicolinate complexes.

A series of zinc dipicolinate (2,6-pyridinedicarboxylate; pdc) complexes [H2tmbpy][Zn(pdc)2]·5H2O () {H2tmbpy = 1,3-bis(4-pyridinium)propane(2+)}, [H2bpy][Zn(pdc)2]·6H2O () {H2bpy = 4,4'-bipyridinium(2+)}, [H2bpy][Zn(pdc)2]·3.5(4np)·2H2O () {4np = 4-nitrophenol}, [H2tmbpy][Zn(pdc)2]·4(2,7dhn)·3H2O () {2,7dhn = 2,7-dihydroxynaphthalene}, [H2bpy][Zn(pdc)2]·2(2,7dhn)·5H2O (), [H2bpy][Zn(pdc)2]·2(pyrogl)·6H2O () {pyrogl = pyrogallol}, and [H2tmbpy][Zn(pdc)2]·2(2,6dhn)·8H2O () {2,6dhn = 2,6-dihydroxynaphthalene} were synthesized and characterised. Different packing patterns in these complexes arise from differences in the abilities of cations to π-stack with zinc dipicolinate units. In , the planar [H2bpy](2+) moieties are π-stacked with adjacent 4,4'-bipyridinium cations and [Zn(pdc)2](2-) anions, whereas in , π-stacks are formed exclusively between [Zn(pdc)2](2-) moieties. 4-Nitrophenol can selectively replace the [H2bpy](2+) cations to form adduct , thus representing a novel host-guest system for molecular recognition of 4-nitrophenol. This recognition does not occur upon treatment of 4-nitrophenol with which bears a nonplanar [H2tmbpy](2+) cation. Host-guest interactions of pyrogallol, 2,6-dihydroxynaphthalene, and 2,7-dihydroxynaphthalene with the parent complexes and were studied, resulting in the crystallization of . The crystal structures of show that guest organic molecules are accommodated in the layers of zinc dipicolinate anions. The formation of different water clusters is also discussed. In addition, topological analysis and classification of the H-bonded patterns driven by strong hydrogen bonds between the [H2bpy](2+) or [H2tmbpy](2+) cations and the [Zn(pdc)2](2-) anions, and organic guest molecules were carried out. This analysis revealed: (i) discrete 0D dimeric (in and ) or tetrameric (in ) motifs with 1M2-1 or 1,3M4-1 topology, respectively, (ii) infinite 1D zigzag chains with 2C1 topology in , and (iii) infinite 2D layers with the hcb [Shubnikov hexagonal plane net/(6,3)] topology in .