A facile and efficient methodology was developed for the synthesis of isoxazole-fused spiropyrrolidine oxindoles 3–5 via a 1,3-dipolar cycloaddition reaction of 3-methyl-4-nitro-5-alkenyl-isoxazoles with azomethine ylides (thermally generated in situ from isatin derivatives and proline or thioproline or sarcosine). Products bearing adjacent quaternary-tertiary centers were smoothly obtained in high yields (up to 90% yield) with good diastereoselectivity (up to 20:1). Furthermore, their biological activity has been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3, human lung cancer cells A549 and human leukemia cells K562 by the MTT-based assays using the commercially available standard drug Cisplatin as a positive control. These results suggested that most of isoxazole-fused spiropyrrolidine oxindoles 3–5 showed considerable cytotoxicities to these three cell lines K562, A549 and PC-3, and that isoxazole-fused spiropyrrolidine oxindoles may be potential leads for further biological screening.

A highly efficient and environmentally benign method for the synthesis of oxindoles featuring two contiguous quaternary carbon centers via an aldol reaction starting from various 3-substituted oxindoles has been established. A wide variety of such featured multi-substituted 1,3-indandione ring-fused 3-oxindole scaffolds were obtained smoothly in good yields (up to 98%) employing the most green of solvents, namely water, as reaction medium. Furthermore, their biological activity has been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3, human lung cancer cells A549 and human leukemia cells K562 by MTT-based assays, using the commercially available standard drug, cisplatin, as a positive control. Gratifyingly, compounds 3s, 3u, 3y and 3c′ exhibited the best levels of in vitro inhibitory activity against human leukemia cells K562, which were almost 2.0, 2.8, 2.5 and 2.2 times, respectively, the activity of the positive control, cisplatin. Compound 3y had 2.7 times the activity of the positive control, cisplatin, against PC-3 cancer cells, and 3s, 3u and 3c′ showed levels of in vitro inhibitory activity against PC-3 cancer cells that were comparable to that of cisplatin. Compounds 3s, 3u and 3y had good inhibitory ability against human lung cancer cells A549. The results indicated that 1,3-indandione ring-fused 3-oxindole analogs may be useful leads for further biological screenings.

A facile and efficient methodology was developed for the synthesis of isoxazole or coumarin-fused 3-quaternary carbon oxindoles and isoxazole-fused pyrrolidinones via DABCO-catalyzed sp3 C–H activation of 5-methyl-isoxazole or 4-methylcoumarin. Furthermore, the biological activity of the isoxazole or coumarin-fused 3-quaternary carbon oxindoles 3 and 5 has been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3 and human leukemia cells K562 by the MTT-based assays using the commercially available standard drug Cisplatin as a positive control. These results suggested that most of the compounds 3 and 5 showed considerable cytotoxicities to these two cell lines K562 and PC-3, and a methyl or an ethyl group of acrylates and an oxindole moiety located in the isoxazole-fused 3-quaternary carbon oxindoles 3 are beneficial for the activity. In addition, the activity of all the afforded isoxazole-fused pyrrolidinones 7 were also evaluated against Gram-positive bacteria Staphylococcus aureus (MTCC96) and Gram-negative bacteria Escherichia coli (ATCC25835) using Penicillin as a standard drug for Gram-positive organism or Streptomycin as standard drug for Gram-negative organism. The results demonstrated that most of the compounds 7 had comparable in vitro inhibitory activity against Gram-positive bacteria Staphylococcus aureus (MTCC96) with the positive control Penicillin. The results also indicated that isoxazole-fused pyrrolidinone analogs had significantly better inhibition ability against Gram-positive bacteria Staphylococcus aureus (MTCC96) than against Gram-negative bacteria Escherichia coli (ATCC25835).

A new methodology was developed for the synthesis of hexahydro-1H-pyrido[2,3-b]indol-2-one scaffolds via a sequential Michael addition/amidation/reductive cyclization process. A wide variety of products bearing a hexahydro-1H-pyrido[2,3-b]indol-2-one core with varying degrees of substitution around it, which is a key structural skeleton found in a large number of biologically active natural products and pharmaceutical compounds, were obtained smoothly with high efficiency (up to overall yield of 67%). Furthermore, their biological activities have been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3, human lung cancer cells A549 and human leukemia cells K562 by the MTT-based assays, using the commercially available standard drug Cisplatin as a positive control. These results suggested there is a trend that lipophilic groups improve the potency, and also suggested a carbonyl moiety located in the hexahydro-1H-pyrido[2,3-b]indol-2-one scaffolds is beneficial for the activity. The results also demonstrated that most of the compounds showed considerable cytotoxicities to these three cell lines K562, A549 and PC-3, and that hexahydro-1H-pyrido[2,3-b]indol-2-one scaffolds may be potential leads for further antitumor activity screenings.

A facile and efficient methodology was developed for the synthesis of multifunctional polycyclic spiropyrrolidine oxindoles bearing mesityl oxide unit via a three-component 1,3-dipolar cycloaddition reaction of dienones 2 with azomethine ylides (thermally generated in situ from isatin derivatives and proline or thioproline). Products bearing adjacent four chiral carbon centers were smoothly obtained in high yields (up to 98% yield) with diastereoselectivities up to >20:1. Furthermore, the key structural characteristic of the products of such a reaction is the natural product ingredient turmerone motif fused at the 3-position of the spirooxindole core, with varying degrees of substitution around it. In addition, their biological activity has been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3, human lung cancer cells A549 and human leukemia cells K562 by the MTT-based assays, using the commercially available standard drugs Cisplatin as a positive control. These results suggested there is a trend that lipophilicity groups improve the potency, and also suggested an mesityl oxide moiety located in the polycyclic spiropyrrolidine oxindoles is beneficial for the activity. The results also demonstrated that most of the compounds showed considerable cytotoxicities to these three cell lines K562, A549 and PC-3, and indicated that polycyclic spiropyrrolidine oxindole analogs bearing mesityl oxide unit may be potential leads for further antitumor activity screenings.

The first phase transfer-catalysed direct γ-substitution of Morita–Baylis–Hillman carbonates of isatins with 3-substituted oxindoles has been developed, which affords 3-alkenyl-oxindole ring-fused 3,3′-disubstituted oxindoles in up to 83% yield under mild reaction conditions. Furthermore, their biological activity has been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3 and human leukemia cells K562, using MTT-based assays with the commercially available standard drug Cisplatin as a positive control. Gratifyingly, compounds 3aa, 3ba and 3ca exhibited comparable in vitro inhibitory activities against human prostate cancer cells (PC-3) to Cisplatin. What's more, 3ba also had a good inhibition ability against human leukemia cells K562. These results indicate that 3-alkenyl-oxindole ring-fused 3,3′-disubstituted oxindole analogs may be potential lead compounds for further biological screening.

A new methodology was developed for the synthesis of spirocyclic oxindoles bearing polyfunctional dihydropyrrole units via an organocatalytic tandem Michael/cyclization sequence. Products bearing adjacent quaternary–tertiary stereocenters were smoothly obtained in high yields (up to 97% yield) with excellent diastereoselectivities up to >20/1.

A highly efficient and environmentally benign method for the synthesis of oxindoles featuring two contiguous quaternary carbon centers via an aldol reaction starting from various 3-substituted oxindoles has been established. A wide variety of such featured multi-substituted 1,3-indandione ring-fused 3-oxindole scaffolds were obtained smoothly in good yields (up to 98%) employing the most green of solvents, namely water, as reaction medium. Furthermore, their biological activity has been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3, human lung cancer cells A549 and human leukemia cells K562 by MTT-based assays, using the commercially available standard drug, cisplatin, as a positive control. Gratifyingly, compounds 3s, 3u, 3y and 3c′ exhibited the best levels of in vitro inhibitory activity against human leukemia cells K562, which were almost 2.0, 2.8, 2.5 and 2.2 times, respectively, the activity of the positive control, cisplatin. Compound 3y had 2.7 times the activity of the positive control, cisplatin, against PC-3 cancer cells, and 3s, 3u and 3c′ showed levels of in vitro inhibitory activity against PC-3 cancer cells that were comparable to that of cisplatin. Compounds 3s, 3u and 3y had good inhibitory ability against human lung cancer cells A549. The results indicated that 1,3-indandione ring-fused 3-oxindole analogs may be useful leads for further biological screenings.

The first phase transfer-catalysed direct γ-substitution of Morita–Baylis–Hillman carbonates of isatins with 3-substituted oxindoles has been developed, which affords 3-alkenyl-oxindole ring-fused 3,3′-disubstituted oxindoles in up to 83% yield under mild reaction conditions. Furthermore, their biological activity has been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3 and human leukemia cells K562, using MTT-based assays with the commercially available standard drug Cisplatin as a positive control. Gratifyingly, compounds 3aa, 3ba and 3ca exhibited comparable in vitro inhibitory activities against human prostate cancer cells (PC-3) to Cisplatin. What's more, 3ba also had a good inhibition ability against human leukemia cells K562. These results indicate that 3-alkenyl-oxindole ring-fused 3,3′-disubstituted oxindole analogs may be potential lead compounds for further biological screening.