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We report herein the design and synthesis of a series of novel tetraethylene glycol‐tethered isatin–1,2,3‐triazole–coumarin hybrids and evaluate their in vitro antitumor activities against seven common human cancer cell lines including drug‐resistant cell line. Results revealed that all the synthesized hybrids showed weak to moderate activities against the tested seven cancer cell lines. The structure–activity relationship was also discussed, and the enriched structure–activity relationship may pave the way for further rationale design of this kind of hybrids. [ABSTRACT FROM AUTHOR]

Herein, we report the design and synthesis of a new set of tetraethylene glycol tethered isatin–coumarin hybrids 7a–l as anticancer agents. Results revealed that all the synthesized hybrids showed no or weak activities against their in vitro antitumor activities against drug‐sensitive HepG2, Hela, A549, DU145, SKOV3, and MCF‐7 as well as drug‐resistant MCF‐7/DOX (doxorubicin‐resistant MCF‐7) human cancer cell lines. The structure–activity relationship was also discussed, and the enriched structure–activity relationship may pave the way for further rationale design of this kind of hybrids. [ABSTRACT FROM AUTHOR]

We report herein the design, synthesis, and antimycobacterial activity of a series of diethylene glycol tethered gatifloxacin–isatin hybrids 5a–o in this paper. Results revealed that all hybrids showed promising activity against both drug‐sensitive and multidrug‐resistant Mycobacterium tuberculosis strains with minimum inhibitory concentration (MIC) in a range of 1–128 μg/mL. Particularly, hybrid 5j with low cytotoxicity in VERO cell line was comparable with the parent gatifloxacin (MIC: 0.78 and 1 μg/mL) against MTB H37Rv and MDR‐TB strains, and ≥32‐fold more potent than isoniazid and rifampicin (MIC: >128 and 32 μg/mL, respectively) against MDR‐TB, suggesting it may serve as a new and promising candidate for further study. [ABSTRACT FROM AUTHOR]

A new class of diethylene glycol tethered moxifloxacin–isatin hybrids 5a–l was designed, synthesized, and evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis (MTB) H37Rv and multidrug‐resistant tuberculosis (MDR‐TB) strains. Our results showed that all hybrids with higher lipophilicity than the parent moxifloxacin exhibited promising activity against the tested strains with minimum inhibitory concentration (MIC) in a range of 0.2–16 μg/mL. In particular, hybrid 5h (MIC: 0.20 and 0.5 μg/mL), which was found to be most active against MTB H37Rv and MDR‐TB, was twofold more potent than isoniazid (MIC: 0.39 μg/mL) against MTB H37Rv and ≥64‐fold more active than isoniazid and rifampicin (MIC: >128 and 32 μg/mL, respectively) against MDR‐TB. [ABSTRACT FROM AUTHOR]

A series of diethylene glycol tethered ciprofloxacin–isatin hybrids 5a–j were designed, synthesized, and evaluated for their in vitro antimycobacterial activity against both drug‐sensitive and multidrug‐resistant (MDR) Mycobacterium tuberculosis strains in this paper. The preliminary results revealed that all hybrids with greater lipophilicity than the parent ciprofloxacin displayed considerable activity against the tested strains with minimum inhibitory concentration (MIC) in a range of 1.56–64 μg/mL. In particular, hybrid 5f (MIC: 1.56 and 2 μg/mL) with low cytotoxicity in VERO cell line was comparable with the parent ciprofloxacin (MIC: 0.78 and 2 μg/mL) against M. tuberculosis H37Rv and MDR tuberculosis strains and ≥16‐fold more potent than isoniazid and rifampicin (MIC: >128 and 32 μg/mL, respectively) against MDR tuberculosis, suggesting that it may serve as a new and promising candidate for further study. [ABSTRACT FROM AUTHOR]

We report herein the design, synthesis, and in vitro anti‐mycobacterial activities of 11 pyrrolidine‐containing or piperazine‐containing nitrofuranylamides. Results revealed that all derivatives 3a–k endowed with excellent activity [minimum inhibitory concentration (MIC): <0.016–0.482 μg/mL] against Mycobacterium tuberculosis (MTB) H37Rv strain and more than half of them were more potent than the first‐line anti‐tuberculosis agents isoniazid (MIC: 0.078 μg/mL) and rifampicin (MIC: 0.078 μg/mL). The most active six derivatives were further evaluated against two clinically isolated multidrug‐resistant MTB strains resistant to both of isoniazid and rifampicin. In particular, four of them 3a, 3c, 3d, and 3j (MIC: 1.412–3.230 μg/mL) showed promising activity against the two clinically isolated multidrug‐resistant MTB strains and could act as starting points for further investigation. [ABSTRACT FROM AUTHOR]

We report herein the design, synthesis, and in vitro anti‐mycobacterial activities of a series of 1,2,3‐triazole‐tetraethylene glycol tethered isatin dimers. Our results indicated that all the synthesized isatin dimers showed weak to moderate anti‐mycobacterial activities against both Mycobacterium tuberculosis H37Rv and multidrug‐resistant tuberculosis strains. Dimer 7g was found to be most active against the tested two strains with minimum inhibitory concentration of 128 and 64 μg/mL, which was eightfold more potent than INH (minimum inhibitory concentration: 512 μg/mL) against multidrug‐resistant tuberculosis. Moreover, dimer 7g (CC50: 62.5 μg/mL) also showed acceptable cytotoxicity against VERO cell line, could act as a lead for further investigation. The enriched structure–activity relationship may pave the way to find more effective anti‐mycobacterial candidates. [ABSTRACT FROM AUTHOR]

A new class of istain dimers tethered by tetraethylene glycol was designed, synthesized, and evaluated for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis H37Rv and multidrug‐resistant M. tuberculosis strains. Our results indicated that all the synthesized hybrids exhibited promising anti‐mycobacterial activities against the tested strains and the enriched structure–activity relationship may pave the way to further rational development of istain dimers with a unique mechanism of action different from that of the currently used drugs to overcome the resistance. [ABSTRACT FROM AUTHOR]

Abstract: A series of diethylene glycol tethered bis‐istain derivatives 4 a‐o were designed, synthesized and screened for their biological activities in this paper. Eight bis‐isatin derivatives displayed broad‐spectrum activities against all tested drug‐sensitive and drug‐resistant cancer cells with IC50 in a range of 8.32 to 49.73 μM. The most active derivative 4 d was >2.5 folds more potent than etoposide against Hela, HCT‐116, A549 and drug‐resistant MCF‐7/DOX (Doxorubicin‐resistant MCF‐7) cells and was comparable to etoposide against DU145, SKOV3 and MCF‐7. Tubulin inhibitory results suggested that this kind of bis‐istain derivatives could exert their anti‐cancer activities through tubulin inhibition. The eight bis‐isatin derivatives with high anti‐tumor activity were selected for further screen to investigate their anti‐mycobacterial and anti‐HIV activities, but the majority of them only exhibited weak to moderate activities. [ABSTRACT FROM AUTHOR]

A series of novel propylene‐1H‐1,2,3‐triazole‐4‐methylene‐tethered isatin‐coumarin hybrids 7a–l that were composed of three anti‐tubercular bioactive substances/pharmacophore coumarin, isatin, and I‐A09 were designed, synthesized, and assessed for their in vitro anti‐tubercular activity against Mycobacterium tuberculosis (MTB) H37Rv. In spite of the hybrids were inactive against the tested MTB H37Rv, the structure–activity relationship was enriched, and these hybrids may act as an ideal starting point for developing new isatin‐coumarin anti‐TB candidates with various linkers. [ABSTRACT FROM AUTHOR]

A new set of ciprofloxacin (CPFX)‐isatin‐1H‐1,2,3‐triazole hybrids 6a–l with greater lipophilicity compared with the parent CPFX was designed, synthesized, and assessed for their invitro anti‐mycobacterial activity against Mycobacterium tuberculosis (MTB) H37Rv as well as cytotoxicity in VERO cell line. The preliminary results showed that all hybrids (MIC: 0.39–50 μg/mL) exhibited promising activities against MTB H37Rv, and six of them (MIC: 0.39–1.56 μg/mL) were more active than the parent CPFX (MIC: 3.12 μg/mL). In particular, the most active conjugate 6h (MIC: 0.39 μg/mL) was comparable with RIF (MIC: 0.39 μg/mL), and eight times more potent than CPFX. All conjugates (CC50: 4–64 μg/mL) were more toxic than the parent (CC50: 128 μg/mL) in VERO cell lines, and the most active hybrids, which also displayed the highest cytotoxicity, should be further optimized. [ABSTRACT FROM AUTHOR]

A new class of isatin‐1,2,3‐triazole‐moxifloxacin (MXFX) hybrids 5a–j was designed, synthesized, and screened for their in vitro antimycobacterial activities against Mycobacterium tuberculosis H37Rv and MDR‐TB. All the synthesized hybrids (MIC: 0.10–0.78 μg/mL) exhibited excellent activities against MTB H37Rv and MDR‐TB, in spite of none of them were more potent than the parent MXFX (MIC: 0.10 and 0.12 μg/mL). Against MTB H37Rv, the most active 5f (MIC: 0.10 μg/mL) was comparable with MXFX and 4 times more potent than RIF (MIC: 0.39 μg/mL). Against MDR‐TB, all hybrids were more active than RIF (MIC: 32 μg/mL) and INH (MIC: >128 μg/mL). In particular, hybrid 5e (MIC: 0.10 μg/mL) was comparable with MXFX and 256 and >1,024 times more potent than RIF and INH. Both conjugates 5e and 5f warrant further investigations. [ABSTRACT FROM AUTHOR]

A new class of propylene‐1H‐1,2,3‐triazole‐4‐methylene‐tethered (thio)semicarbazone‐isatin‐moxifloxacin hybrids 6a–h was designed, synthesized, and screened for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis (MTB) H37Rv and MDR‐TB as well as cytotoxicity in VERO cell line. All the synthesized hybrids (MIC: 0.05–2.0 μg/mL) exhibited excellent activities against M. tuberculosis H37Rv and MDR‐TB; in particular, conjugate 6c (MIC: 0.05 and 0.12 μg/mL) was no inferior to the three references MXFX (MIC: 0.10 and 0.12 μg/mL), RIF (MIC: 0.39 and 32 μg/mL), and INH (MIC: 0.05 and >128 μg/mL) against the tested two strains. All hybrids (CC50: 2–8 μg/mL) were much more cytotoxic than the parent MXFX (CC50: 128 μg/mL) should be further optimized. [ABSTRACT FROM AUTHOR]

A new class of 1 H-1,2,3-triazole-tethered 8-OMe ciprofloxacin (8-OMe CPFX) isatin hybrids 5a-l was designed, synthesized and screened for their in vitro anti-mycobacterial activities against Mycobacterium tuberculosis H37Rv and multi-drug-resistant tuberculosis (MDR-TB). All targets (minimum inhibitory concentration (MIC): 0.20-8.0 μg/mL) exhibited promising inhibitory activity against MTB H37Rv and MDR-TB. Among them, conjugate 5h (MIC: 0.20 μg/mL), was 2-16 times more potent in vitro than the references CPFX (MIC: 3.12 μg/mL), 8-OMe CPFX (MIC: 1.56 μg/mL) and RIF (MIC: 0.39 μg/mL) against MTB H37Rv. The most potent hybrid 5l (MIC: 0.25 μg/mL) was 8-256 times more active than the three references (MIC: 2.0-64 μg/mL) against MDR-TB. Both of them warrant further investigations. [ABSTRACT FROM AUTHOR]