Design and Synthesis of 3,4-Dihydropyrrolo[2, 1-c][1, 4]oxazin-1-oneand its 7-Acyl Derivatives

Starting from 1H-pyrrole, unreported 3, 4-dihydropyrrolo[2, 1-c][l, 4]oxazin-1-one 4, 7-(4-chlorobenzoyl)-3, 4-dihydropyrrolo[2, 1-c][1, 4]oxazin-1-one 5 and 7-benzoyl-3, 4-dihydro-pyrrolo [2, 1-c][1, 4]oxazin-1-one 9 were designed and synthesized. They may have antipyretic and analgesic activities.

Synthesis and antiviral activities of novel 1,4-pentadien-3-one derivatives bearing an emodin moiety

A series of 1,5-diaryl-1,4-pentadien-3-one derivatives bearing an emodin group were designed and synthesized by the combination of natural products. The antiviral activities against tobacco mosaic virus（TMV） and cucumber mosaic virus（CMV） in vivo were evaluated. Some of the derivatives displayed promising curative effect and protective activity against TMV. Compound D5 showed appreciable curative bioactivity on TMV approximately of 50% at 306.2 mg/m L, which was superior to ningnanmycin（409.3 mg/m L）.

Design, synthesis, and biological evaluation of quinazolin-4(3H)-one derivatives co-targeting poly (ADP-ribose) polymerase-1 and bromodomain containing protein 4 for breast cancer therapy

This study was aimed to design the first dual-target small-molecule inhibitor co-targeting poly(ADP-ribose)polymerase-1(PARP1)and bromodomain containing protein 4(BRD4),which had important cross relation in the global network of breast cancer,reflecting the synthetic lethal effect.A series of new BRD4 and PARP1 dual-target inhibitors were discovered and synthesized by fragmentbased combinatorial screening and activity assays that together led to the chemical optimization.Among these compounds,19 d was selected and exhibited micromole enzymatic potencies against BRD4 and PARP1,respectively.Compound 19 d was further shown to efficiently modulate the expression of BRD4 and PARP1.Subsequently,compound 19 d was found to induce breast cancer cell apoptosis and stimulate cell cycle arrest at G1 phase.Following pharmacokinetic studies,compound 19 d showed its antitumor activity in breast cancer susceptibility gene 1/2(BRCA1/2)wild-type MDA-MB-468 and MCF-7 xenograft models without apparent toxicity and loss of body weight.These results together demonstrated that a highly potent dual-targeted inhibitor was successfully synthesized and indicated that co-targeting of BRD4 and PARP1 based on the concept of synthetic lethality would be a promising therapeutic strategy for breast cancer.

Design, synthesis and MAO inhibitory activity of 2-(arylmethylidene)-2,3-dihydro-1-benzofuran-3-one derivatives

A series of 2-（arylmethylidene）-2,3-dihydro-1-benzofuran-3-one derivatives（aurones, 1–20） were synthesized and screened for their inhibitory activity against h MAO. Seventeen compounds（1–5, 7–17,19） were found to be selective towards h MAO-B, while two were non-selective（6 and 20） and one（18）selective towards h MAO-A. Compound 17（Ki = 0.10 0.01 mmol/L） was found to be equally potent and selective towards h MAO-B, when compared with the standard drug Selegiline（Ki = 0.12 0.01 mmol/L）.Nature and position of substitution in aryl ring at 2nd position of benzofuranone influences h MAO-B inhibitory potency, while their structural bulkiness influences selectivity between h MAO-A and h MAO-B.Molecular docking simulation was also carried out to understand the interaction of inhibitor with the enzyme at molecular level, and we found the docking results were in good agreement with the experimental values. Comparison of the activity profile of the aurones with their corresponding flavones reported earlier by our group revealed that there exists no difference in potency as well as selectivity.