Ming-Liang Ma

Coordination-Driven Self-Assembly of a Discrete Molecular Cage and an Infinite Chain of Coordination Cages Based on ortho-Linked Oxacalix[2]benzene[2]pyrazine and Oxacalix[2]arene[2]pyrazine

Coordination-driven self-assembly of ortho-linked oxacalix[2]benzene[2]pyrazine (1) as well as oxacalix[2]arene[2]pyrazine (2) with a silver cation resulted in the formation of a discrete molecular cage (3) and a one-dimensional chain of coordination cages (4), respectively. Single crystal X-ray diffraction analysis confirmed the structures of 3 and 4. The silver ions in 3 adopted tetrahedral coordination geometries while the silver ions in 4 adopted square-planar coordination geometries. The void of the metal-containing cage 3 was occupied by a methyl group of an acetonitrile bonded to a neighboring cage in the solid state, and one benzene ring was found to reside in the void of each cage of complex 4.

Therapeutic Melting Pot of Never in Mitosis Gene A Related Kinase 2 (Nek2): A Perspective on Nek2 as an Oncology Target and Recent Advancements in Nek2 Small Molecule Inhibition

The global incidence of cancer is on the rise, and within the next decade, the disease is expected to become the leading cause of death worldwide. Forthcoming strategies used to treat cancers focus on the design and implementation of multidrug therapies to target complementary cancer specific pathways. A more direct means by which this multitargeted approach can be achieved is by identifying and targeting interpathway regulatory factors. Recent advances in understanding Nek2 (NIMA related kinase 2) biology suggest that the kinase potentially represents a multifaceted therapeutic target. In this regard, pharmacologic modulation of Nek2 with a single agent may effect several mechanisms important for tumor growth, survival, progression, and metastasis. We herein review the development of Nek2 as an oncology target and provide a succinct chronology of drug discovery campaigns focused on targeting Nek2.

Synthesis, structure, and conformation of terphenylene-derived azacalix[4]aromatics

Abstract Several novel azacalix[4]aromatics constituting terphenylene units have been synthesized via sequential nucleophilic aromatic substitution reactions of 5′-t-butyl-(1,1′:3′,1″-terphenyl)-3,3″-diamine 9 and 5′-t-butyl-(1,1′:3′,1″-terphenyl)– 4,4″-diamine 11 with 1,5-difluoro-2,4-dinitrobenzene and cyanuric chloride, respectively. The bridging –NH– functions of the tetra-nitro substituted azacalix[2]arene[2]terphenylenes 1 and 2 have been transformed to the corresponding –N(CH3)– bridged azacalix[2]arene[2]terphenylenes 3 and 4 via N-alkylation. Single crystal X-ray analysis revealed that the terphenyl-3,3″-diamine derived azacalix[2]terphenylene[2]triazine 5 adopts a distorted chair conformation in the solid state, and the terphenyl-4,4″-diamine derived azacalix[2]terphenylene[2]triazine 6 was found to adopt a 1,3-alternate conformation.

Silver-mediated self-assembly of metallosupramolecular networks based on pyrimidine-containing oxacalix[n]aromatics

Under self-assembly conditions, the interaction between pyrimidinyl-containing oxacalixaromatics (1 and 2) and silver cation resulted in the formation of two-dimensional coordination networks 3 and 4; single crystal X-ray analysis revealed that complex 3 featured a coordination polymeric structure with ligand 1 arranged in an offset manner along the polymeric chain, while network 4 featured a structure with regular microcyclic channels.

Carboxylic Acid-Derived Oxacalix[2]arene[2]pyrazine Self-Assembles into Unprecedented Diamondoid Networks

A 1,3-alternate conformational oxacalix[2]arene[2]pyrazine, 1, made up of two tetrahedrally oriented –COOH functions and two upper rim pyrazinyl nitrogen atoms, self-assembles into an unprecedented six-fold interpenetrated diamondoid network via intermolecular hydrogen bond interactions. Disordered guest molecules could be included in the hydrophobic channels presented in the supramolecular aggregates.

Trigonal prismatic bicyclocalixaromatics, synthesis and structures

Two trigonal prismatic bicyclooxacalixarenes 1 and 2 were obtained by condensation reaction of 1,3,5-tri(p-hydroxyphenyl)benzene and 2,4,6-tri(p-hydroxyphenyl)triazine, respectively, with 1,5-difluoro-2,4-dinitrobenzene. Single crystal structural analysis revealed that the bicyclooxacalixarene 1 adopts a distorted triangular prismatic structure. Bicyclooxacalixarene 2, however, possesses an almost D 3 h symmetric triangular prismatic structure. The colorimetric changes in the acetone solutions of 1 or 2 upon addition of certain anions have been found highly relevant to the nitro-substituents in the phenyl pillars, not to their macrocyclic structures.

Preclinical activity of MBM-5 in gastrointestinal cancer by inhibiting NEK2 kinase activity

NEK2 is a conserved mitotic regulator critical for cell cycle progression. Aberrant expression of NEK2 has been found in a variety of human cancers, making it an attractive molecular target for the design of novel anticancer therapeutics. In the present study, we have identified a novel compound MBM-5, which was found to bind to NEK2 with high affinity by docking simulations study. MBM-5 potently inhibited NEK2 kinase activity in vitro in a concentration-dependent manner. MBM-5 also suppressed cellular NEK2 kinase activity, as evidenced by the decreased phosphorylation of its substrate Hec1 on S165 in a concentration- and time-dependent manner. This inhibition impeded mitotic progression by inducing chromosome segregation defects and cytokinesis failure; therefore leading to accumulation of cells with ≥4N DNA content, which finally underwent apoptosis. More importantly, MBM-5 treatment effectively suppressed the tumor growth of human gastric and colorectal cancer cells xenografts. Taken together, we demonstrated that MBM-5 effectively inhibited the kinase activity of NEK2 and showed a potential application in anti-cancer treatment regimens.

Diastereoselective synthesis of isochromans via the Cu(II)-catalysed intramolecular Michael-type trapping of oxonium ylides

A highly diastereoselective approach for the rapid construction of an isochroman skeleton was achieved by the copper(ii)-catalyzed transformation of alcohol-tethered enones and diazo compounds. This transformation was proposed to proceed through the intramolecular Michael-type trapping of an in situ generated oxonium ylide intermediate. The copper(ii) catalyst may play a dual role in catalyzing diazo decomposition as well as activating the enone unit. With this method, a series of 3,4-substituted isochromans were obtained with excellent diastereoselectivities under very mild reaction conditions.