Aixi Hu

One-Pot Three-Component Synthesis of Novel Diethyl((2-oxo-1,2-dihydroquinolin-3-yl)(arylamino)methyl)phosphonate as Potential Anticancer Agents

With the aim of discovering new anticancer agents, we have designed and synthesized novel α-aminophosphonate derivatives containing a 2-oxoquinoline structure using a convenient one-pot three-component method. The newly synthesized compounds were evaluated for antitumor activities against the A549 (human lung adenocarcinoma cell), HeLa (human cervical carcinoma cell), MCF-7 (human breast cancer cell), and U2OS (human osteosarcoma cell) cancer cell lines in vitro, employing a standard 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The results of pharmacological screening indicated that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most compounds showed more potent inhibitory activities comparable to 5-fluorouracil (5-FU) which was used as a positive control. The mechanism of representative compound 4u (diethyl((2-oxo-1,2-dihydroquinolin-3-yl)(phenyl-amino)methyl)phosphonate) indicated that the compound mainly arrested HeLa cells in S and G2 stages and was accompanied by apoptosis in HeLa cells. This action was confirmed by acridine orange/ethidium bromide staining, Hoechst 33342 staining, and flow cytometry.

Design and Synthesis of 4-Alkyl-2-amino(acetamino)-6-aryl-1,3-thiazine Derivatives as Influenza Neuraminidase Inhibitors.

With a convenient and economical method, two series of 1,3‐thiazine derivatives 1 and 2 were synthesized, and their neuraminidase (NA) inhibitory activities were evaluated. The pharmacological results showed that most of the compounds have potent NA inhibitory activity. Especially, 1g exhibited the best activity against influenza virus A (H1N1) NA (IC50 = 29.06 µg/mL), and its crystal structure was determined by single‐crystal X‐ray diffraction. The preliminary biological assay indicated that 1,3‐thiazine could be used as a core structure to design novel influenza NA inhibitors.

Synthesis and fungicidal activity of some novel thiazole Schiff bases derived from benzo[d][1,3]dioxole

A series of novel thiazole Schiff base derivatives containing benzo[d][1,3]dioxole moiety was designed, synthesized and screened for their fungicidal activities. The preliminary results demonstrated that compounds 6p, 6q and 6r possessed potent activities against Phytophthora infestans, Pyricularia oryzae and Septoria tritici in vitro. Compounds 6d and 6r exhibited remarkable activities against Botrytis cinerea(whole plant) and Phytophthora infestans(leaf disk) respectively in vivo, which were identified as the most promising candidates for further study and could be used as possible lead compounds for developing new fungicides.

Synthesis and antitumor evaluation of 5-(benzo[d][1,3]dioxol-5-ylmethyl)-4-(tert-butyl)-N-arylthiazol-2-amines

A series of novel N-aryl-5-(benzo[d][1,3]dioxol-5-ylmethyl)-4-(tert-butyl)thiazol-2-amines (C1–C31) were synthesized and evaluated for their antitumor activities against HeLa, A549 and MCF-7 cell lines. Some tested compounds showed potent growth inhibition properties with IC50 values generally below 5 μM against the three human cancer cells lines. Compound C27 showed potent activities against HeLa and A549 cell lines with IC50 values of 2.07 ± 0.88 μM and 3.52 ± 0.49 μM, respectively. Compound C7 (IC50 = 2.06 ± 0.09 μM) was the most active compound against A549 cell line, while compound C16 (IC50 = 2.55 ± 0.34 μM) showed the best inhibitory activity against the MCF-7 cell line. The preliminary mechanism of the inhibitory effect was investigated via further experiments, such as morphological analysis by dual AO/EB staining and Hoechst 33342 staining, and cell apoptosis and cycle assessment by FACS analysis. The results illustrated that compound C27 could induce apoptosis and cause both S-phase and G2/M-phase arrests in HeLa cell line. Therefore, compound C27 could be developed as a potential antitumor agent.

2-Ethyl-6-methyl­anilinium 4-methyl­benzene­sulfonate

The title compound, C9H14N+·C7H7SO3 −, contains a 2-ethyl-6-methylanilinium cation and a 4-methylbenzenesulfonic anion. The cations are anchored between the anions through N—H⋯O hydrogen bonds. Electrostatic and van der Waals interactions, as well as hydrogen bonds, maintain the structural cohesion.

Design, Synthesis, and Antitumor Activity of (E,Z)-1-(dihydrobenzofuran-5-yl)-3-phenyl-2-(1,2,4-triazol-1-yl)-2-propen-1-ones.

A series of (E,Z)‐1‐(dihydrobenzofuran‐5‐yl)‐3‐phenyl‐2‐(1,2,4‐triazol‐1‐yl)‐2‐propen‐1‐ones (C1–C35) were designed and synthesized, and the structures of compounds (Z)‐C27 and (Z)‐C29 were confirmed by single‐crystal X‐ray diffraction. The antitumor activities of these novel compounds against cervical cancer (HeLa), lung cancer (A549), and breast cancer (MCF‐7) cell lines were evaluated in vitro. Majority of the title compounds exhibited strong antitumor activities and were much more promising than the positive control Taxol, which were also accompanied by lower cytotoxicity to normal cells. In particular, compounds (E,Z)‐C24 exhibited the most consistent potent activities against three neoplastic cells with IC50 values ranging from 3.2 to 7.1 μm. Further researches demonstrated that compounds (E,Z)‐C24 could induce cell apoptosis and arrest cell cycle at the G2/M and S phases. Meanwhile, the structure–activity relationship between the configurations and cytotoxicity of the compounds was also investigated.

Synthesis and antitumor activity of 4-tert-butyl-5-benzyl-2-benzyliminothiazoles

A series of novel Schiff bases including 4-tert-butyl-5-benzyl-2-benzyliminothiazoles was synthesized by reacting the aromatic aldehydes with the corresponding 2-aminothiazoles. The antitumor bioassay revealed that compounds 2n and 2m exhibited potent cytotoxicity against human cervix cancer(HeLa) cell line with IC50 values of 0.001 and 0.007 mmol/L, respectively. The preliminary structure-activity relationship(SAR) investigations and the apoptosis evaluation suggest that 4-tert-butyl-5-benzyl-2-benzyliminothiazoles may be a satisfactory backbone for antitumor activity, and compound 2n can serve as an attractive candidate for the development of novel apoptosis in anticancer treatment.

Synthesis and evaluation of 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides as COX-2 and serotonin reuptake inhibitors.

Based on the positive effects of COX‐2 inhibitors on depressive symptoms and the desirable physicochemical and biological properties of the morpholine group, a series of novel 2‐(2‐arylmorpholino)ethyl esters of ibuprofen hydrochlorides were designed, synthesized, and tested for their COX‐2 inhibitory and serotonin reuptake inhibitory activities in vitro. The structure–activity relationships of the 2‐(2‐arylmorpholino)ethyl esters of ibuprofen hydrochlorides as dual COX‐2 and serotonin reuptake inhibitors were determined and discussed in detail. The biological assays indicated that five of the compounds possess good COX‐2 selectivity (selectivity index COX‐1/COX‐2 42.8–158.1). The compound 2‐[2‐(4‐benzyloxyphenyl)morpholino]ethyl 2‐(4‐iso‐butylphenyl)‐propanoate hydrochloride (1k) shows better COX‐2 inhibitory activity (IC50 = 0.78 µM) than ibuprofen (IC50 = 7.6 µM), and it simultaneously possesses favorable serotonin reuptake inhibitory activity.

5,5′-(1,3-Phenylenedimethylene)bis(2-amino-4-tert-butylthiazol-3-ium) dibromide monohydrate

Geometric parameters of the title salt, C22H32N4S22+·2Br−·H2O, are in the usual ranges. The crystal packing is stabilized by N–H⋯O, N–H⋯Br and O–H⋯Br hydrogen bonds.

Design and one-pot synthesis of 2-thiazolylhydrazone derivatives as influenza neuraminidase inhibitors

Two series of novel 2-thiazolylhydrazone derivatives were designed and synthesized via one-pot reaction of benzaldehyde derivatives,