ABSTRACT
This review discusses chiral-at-metal complexes and introduces enantiomorphs from assembly structure. Owing to the diverse coordination number and activity of metal ions as chiral centers, abundant structures for chiral selectivity, catalysis, and polarized light-response are the notable advantages of the chiral-at-metal complexes. The rational design and preparation of linear multi-dentate ligands is a good choice to improve the stability of chiral complexes, such as multi-bonding structure for high stability as a self-limiting system. The bio-significance and potential application of chiral-at-metal complexes are discussed, such as the synergistic effect of catalysis and chiral selectivity of the metal center in enzymes. Enzyme could be remolded to replace the original central metal ions with highly active rare earth or precious metal ions to form artificial metalloenzyme or to remove the "redundant" part around the metal center to improve the accessibility of substrate. The polarized light-response mechanism of chiral opsin is introduced in relation to its role in animal migration. Metal-organic frameworks (MOFs) are crystalline and porous materials built from metal nodes or clusters and organic linkers and provide the possibility to prepare artificial enantiomorphs. The preparations, applications, and characterization methods of MOF enatiomorphs are therefore introduced. We hope this review inspires researchers at all levels of their career to consider the title topic in their own research in terms of its application and potential value.
ABSTRACT
A series of new diarylpyrimidines (DAPYs) characterized by a halogen atom on the methylene linker between wing I and the central pyrimidine ring was synthesized and evaluated for their anti-HIV activity in MT-4 cell cultures. The two most promising compounds 7f and 7g showed excellent activity against wild-type HIV-1 with low nanomolar EC50 values of 0.005 and 0.009 µM, respectively, which were comparable to or more potent than all the reference drugs zidovudine (AZT), lamivudine (3TC), nevirapine (NEV), efavirenz (EFV), delaviridine (DLV) and etravirine (ETV). In particular, 7g also displayed strong activity against the double mutant strain 103N + 181C with an EC50 value of 8.2 µM. The preliminary structure-activity relationship (SAR) and molecular docking analysis of this new series of CHX-DAPYs were also investigated.
Subject(s)
Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacology , Benzamides/chemical synthesis , Benzamides/pharmacology , Drug Design , HIV Reverse Transcriptase/antagonists & inhibitors , Pyrimidines/pharmacology , Reverse Transcriptase Inhibitors/chemical synthesis , Reverse Transcriptase Inhibitors/pharmacology , Cell Survival/drug effects , Cells, Cultured , HIV-1/drug effects , Humans , Models, Molecular , Molecular Docking Simulation , Molecular Structure , Nitriles , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/virology , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Structure-Activity Relationship , Tumor Cells, Cultured , Virus Replication/drug effectsABSTRACT
A series of CR2(OH)-diarylpyrimidine derivatives (CR2(OH)-DAPYs) featuring a hydrophobic group at CH(OH) linker between wing I and the central pyrimidine were synthesized and evaluated for their anti-HIV activity in MT-4 cell cultures. All the target compounds except for compound 3k displayed inhibitory activity against HIV-1 wild-type with EC50 values ranging from 7.21±1.99 to 0.067±0.006 µM. Among them, compound 3d showed the most potent anti-HIV-1 activity (EC50=0.067±0.006 µM, SI>592), which was approximately 2-fold more potent than the reference drugs nevirapine (NVP) and delaviridine (DLV) in the same assay. In addition, the binding modes with HIV-1 RT and the preliminary SAR studies of these new derivatives were also investigated.
Subject(s)
HIV Reverse Transcriptase/antagonists & inhibitors , HIV-1/enzymology , Reverse Transcriptase Inhibitors/chemistry , Binding Sites , Cell Line , HIV Reverse Transcriptase/metabolism , Humans , Molecular Docking Simulation , Protein Structure, Tertiary , Pyrimidines/chemistry , Pyrimidines/metabolism , Reverse Transcriptase Inhibitors/metabolism , Structure-Activity RelationshipABSTRACT
A series of C6-rigid S-DABO analogs characterized by a substituted benzoyl group at C6 position of the pyrimidine ring has been synthesized and biological evaluation as NNRTIs against wild-type HIV-1 strain IIIB, double RT mutant (K103N+Y181C) strain RES056 as well as HIV-2 strain ROD in MT-4 cell cultures. Most of the compounds exhibited moderate antiviral activities. Among them, compound 7q displayed the highest anti-HIV-1 activity with an EC50 value of 0.26µM and a selectivity index (SI) of 541. The preliminary structure-activity relationship (SAR) of these new S-DABOs was investigated, the target RT was confirmed and docking study was performed.
