A series of novel hybrid structure derivatives, containing both LEE011 and Cabozantinib pharmacophore, were designed, synthesized and evaluated. Surprisingly, a compound 4d was discovered that highly exhibited effective and selective activity of CDK9 inhibition with IC50 = 12 nM. It effectively induced apoptosis in breast and lung cancer cell lines at nanomolar level. Molecular docking of 4d to ATP binding site of CDK9 kinase demonstrated a new hydrogen bonding between F atom of 4-(3-fluorobenzyloxy) group and ASN116 residue, compared with the positive control, LEE011. The compound 4d could block the cell cycle both in G0/G1 and G2/M phase to prevent the proliferation and differentiation of cancer cells. Mice bared-breast cancer treated with compound 4d showed significant suppression of cancer with low toxicity. Taken together, this novel compound 4d could be a promising drug candidate for clinical application.A series of novel hybrid structure derivatives, containing both LEE011 and Cabozantinib pharmacophore, were designed, synthesized and evaluated. Surprisingly, a compound 4d was discovered that highly exhibited effective and selective activity of CDK9 inhibition with IC50 = 12 nM. It effectively induced apoptosis in breast and lung cancer cell lines at nanomolar level. The compound 4d could block the cell cycle both in G0/G1 and G2/M phase to prevent the proliferation and differentiation of cancer cells. Mice bared-breast cancer treated with compound 4d showed significant suppression of cancer with low toxicity.Download high-res image (99KB)Download full-size image

•A polymorph and a pseudopolymorph of N,N-di(n-octyl)quinacridone (DOQA) are prepared.•Two forms show different molecular packing structures.•Different morphologies and luminescent properties of two forms are exhibited.•DOQA was employed as building blocks to fabricate luminescent microscale wires.A polymorph A and a pseudopolymorph B of N,N-di(n-octyl)quinacridone (DOQA) have been prepared by altering the crystal growth conditions and their molecular structures have been identified by single-crystal X-ray diffraction. Both polymorphs show similar characteristics of molecular structures and their molecular arrangements are characterized by the intermolecular π…π interactions and CH…O hydrogen interactions. Due to the presence of methanol molecules in the form B, it is found that in crystalline polymorphs A and B the distance and the degree of overlap of π-electron are remarkably different. Simultaneously, molecules of two forms show different hydrogen bonding patterns. The different molecular packing structures result in significantly different morphologies, namely block shape for A whereas needle shape for B, and solid-state luminescent properties of two forms. From the X-ray single-crystal analysis, the obvious different molecular packing structures of two forms, due to the presence of methanol molecules in the form B, urge us to investigate the phase-dependent emission properties of DOQA in microstructures. DOQA can be employed as building blocks to fabricate luminescent microscale wires by controlling the ratio of methanol solvent.Graphical abstractThe crystallization of DOQA affords a polymorph A and a pseudopolymorph B. Both polymorphs show similar characteristics of molecular structures and their molecular arrangements are characterized by the intermolecular π…π interactions and CH…O hydrogen interactions. It is found that, due to the presence of methanol molecules in the form B, the distance and the degree of overlap of π-electron are remarkably different in crystalline polymorphs A and B. Simultaneously, molecules of two forms show different hydrogen bonding patterns. The different molecular packing structures result in significantly different emission properties and different morphologies of two polymorphs, namely, block shape for A whereas needle shape for B. From the X-ray single-crystal analysis, the obvious different molecular packing structures of two forms urge us to investigate the phase-dependent emission properties of DOQA in microstructures. DOQA can be employed as building blocks to fabricate luminescent microscale wires by controlling the ratio of methanol solvent.