One-pot synthesis of substituted pyrrole-imidazole derivatives with anticancer activity.

A facile and efficient method to synthesize pyrrole-imidazole was developed via a post-Ugi cascade reaction followed by one purification procedure. Synthesized pyrrole-imidazole was collected by performing a mild reaction and a simple procedure, which could be applicable to a broad scope of functionalized anilines. The screening results demonstrated that compound 7e exhibited a high potency of anticancer activity in human pancreatic cancer cell lines PANC and ASPC-1. Our work shed light on the potential of post-Ugi cascade reaction in combinatorial and medicinal chemistry.

Efficacy and safety of recombinant human lymphotoxin-α derivative with cisplatin and fluorouracil in patients with metastatic esophageal squamous cell carcinoma: A randomized, multicenter, open-label, controlled, phase 2b trial.

BACKGROUND: Recombinant human lymphotoxin-α derivative (rhLTα-Da) is a lymphotoxin-α derivative that is missing 27 N-terminal amino acid residues. Previous studies indicated a benefit from the addition of rhLTα-Da to cisplatin-based treatment in patients with metastatic esophageal squamous cell carcinoma. The current study was conducted to evaluate the efficacy and safety of rhLTα-Da plus cisplatin and fluorouracil (PF) in patients with mESCC. METHODS: Patients from 15 centers in China were randomly assigned (1:1:1) to 3 arms (arm A, PF plus 10 µg/m2 daily rhLTα-Da; arm B, PF plus 20 µg/m2 daily rhLTα-Da; arm C, PF alone). The primary endpoints included progression-free survival (PFS) and the confirmed overall response rate (ORR). An exploratory analysis was performed to evaluate the role of serum tumor necrosis factor receptor II (TNFR II) in predicting the efficacy of rhLTα-Da. RESULTS: Between September 2010 and May 2013, 150 patients were enrolled. No significant differences in either PFS or ORR were observed between the 3 arms. However, in a small subset of patients who had low serum TNFR II levels, the median PFS was significantly longer for those in arm B than for these in other 2 arms (7.2 months [95% confidence interval, 5.1-8.6 months] for arm B vs 3.5 months [95% confidence interval, 1.7-5.5 months] for arm A [P = .022] and 4.0 months [95% confidence interval, 3.2-6.3 months] for arm C [P = .027]). The addition of rhLTα-Da significantly increased the incidence of chills (P < .001). CONCLUSIONS: rhLTα-Da combined with the PF regimen failed to improve PFS and ORR in patients with mESCC, except in a small subset that had low serum TNFR II concentrations. Cancer 2017;123:3986-94. © 2017 American Cancer Society.

An Efficient and Facile Method for the Synthesis of Benzimidazoisoquinoline Derivatives via a Multicomponent Reaction.

Two series of benzimidazoisoquinoline and fused benzimidazoisoquinoline-benzimidazole derivatives have been synthesized using an efficient one-pot procedure. This process involves an intramolecular nucleophilic substitution reaction and provides facile access to two series of complexes and potentially interesting biologically active scaffolds.

[Role of HO/CO in IL-beta induced pancreatic islets apoptosis and the effect of fructose-1, 6-disphosphate].

AIM: To investigate the protective role of HO/CO systems in IL-1beta induced islest apoptosis and to explore the mechanisms of the protective effect of fructose-1, 6-disphosphate (FDP). METHODS: The pancreases of the rats were removed to collect islets cells. The cells were incubated with IL-1beta with/or FDP. Cell activity, insulin secretion, HO-1 activity, CO content and apoptotic percentage were detected. RESULTS: HO-1 activity and CO content of the normal control group were low. IL-1beta induced a significant decrease of cell activity and insulin release, flow cytometry analysis showed that apoptotic percentage of islet cells remarkably increased following the addition of IL-1beta, FDP obviously improved the islets cellular activity damaged by IL-1beta, and basic amount of insulin secretion and stimulated by high glucose were improved (P < 0.01). Content of CO and activity of HO-1 were higher in the IL-1beta group than the normal control group (P < 0.05), and there were significant differences between the FDP groups and IL-1beta group. FDP decreased cell apoptotic percentage. Activities of HO-1 and content of CO were higher than that in the IL-1beta group (P < 0.01). CONCLUSION: FDP can attenuate the IL-1beta induced apoptosis of cultured beta cells, the mechanism of which may be improved HO-1 activity and CO content.

Systemic ischemic preconditioning plus hemodilution enhanced early functional recovery of reperfused heart in the rabbits.

We investigated whether transient systemic ischemia can precondition the heart against the ensuing ischemic insult. Rabbits were randomly divided into systemic ischemic preconditioning (SIP), hemodilution (HD) and control (C) groups. SIP was induced by rapidly withdrawing blood from femoral artery and maintaining the mean artery pressure at 50 mmHg for 10 min. Afterwards, 50% of the withdrawn blood was re-infused with equal volumes of 6% deferoxamine-conjugated hydroxyethyl-starch (D-HES). Hemodilution in HD group was achieved by withdrawing blood at 8 ml/kg accompanied by concomitant infusion of equal volumes of D-HES. Animals were subjected to 30 min of coronary artery occlusion followed by 120 min of reperfusion. Cardiac output (CO) (thermodilution method), plasma malondialdehyde and nitric oxide content were measured at baseline and until 120 (R120) min of reperfusion. At R120, CO in group-C was significantly lower than its baseline value, accompanied by a significant reduction in nitric oxide production and increase in malondialdehyde concentration; CO in group-SIP and group-HD maintained at baseline levels throughout reperfusion. At R120, CO in group-SIP, but not in group-HD, was significantly higher than that in group-C. It is concluded that transient SIP followed by hemodilution with D-HES facilitates early functional recovery of the ischemic-reperfused rabbit hearts.