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Chlorophyll a exhibits excellent photosensitive activity in photosynthesis. The unstability limited its application as photoensitizer drug in photodynamic therapy. Here a series of novel chlorophyll a degradation products pyropheophorbide-a derivatives were synthesized and evaluated for lung cancer in PDT. These compounds have strong absorption in 660–670 nm with high molar extinction coefficient, and fluorescence emission in 660–675 nm upon excitation with 410–415 nm light. They all have much higher ROS yields than pyropheophorbide-a, and compound 10 was even higher than [3-(1-hexyloxyethyl)]-pyrophoeophorbide a (HPPH). Distinctive phototoxicity was observed in vitro and the inhibition effect was in light dose-dependent and drug dose-dependent style. They can effectively inhibit the growth of lung tumor in vivo. Among them, compound 8 and 11 have outstanding photodynamic anti-tumor effects without obvious skin photo-toxicity, so they can act as new drug candidates for photodynamic therapy.

Photodynamic therapy (PDT) has been developed as a promising therapeutic method in cancer treatment. The discovery of effective photosensitizer, which is the key factor of PDT, is highly desired. This paper reports the synthesis of novel chlorin derivatives, 5,10,15,20-tetraphenyl-[2:3]-[(methoxycarbonyl, carboxy)methano] chlorin I and 5,10,15,20-tetraphenyl-[2:3]- {[methoxycarbonyl, (2-hydroxyethyl)amide]methano}chlorin II. Their structures were characterized with UV–vis, 1HNMR, 13CNMR and HRMS spectroscopies. Photophysical and photochemical experiments results showed that compound I and II had an absorption maximum around 650 nm, with molar extinction coefficients of 1 × 104 M−1 cm−1. They had strong fluorescence emission in 650–660 nm upon excitation with 419–422 nm light. ESR showed that singlet oxygen was produced upon irradiation of compounds with 650 nm light in the presence of molecular oxygen. The photo-bleaching test indicated that the structure of compounds was stable. These new compounds exhibit excellent anti-tumor effects and lower toxicity compared to m-THPC in vitro and in vivo. Compound I and II had high tumor selectivity, which could induced tumor cells shrinkage and necrosis under 650 nm laser irradiation. Flow cytometry revealed that the compounds might mediate PDT effect at late apoptotic phase. These results make these compound I and II promising candidates for future study in photo-diagnosis and photodynamic therapy of cholangiocarcinoma.

A series of new 6-substituted aminocarbonyl benzimidazole derivatives with 1, 4-disubsituted or 1, 5-disubsituted indole moiety and benzoic acid moiety were designed, synthesized and pharmacologically evaluated. Most of the synthesized compounds could bind to the AT

Effective photosensitizers are particularly important factor in clinical photodynamic therapy (PDT). However, there is a scarcity of photosensitizers for simultaneous cancer photo-diagnosis and targeted PDT. Herein, two novel dimethyl 2-(guanidinyl)ethylamino chlorin e

A series of new angiotensin II (Ang II) receptor 1 antagonists were designed, synthesized and evaluated. All compounds showed nanomolar affinities for the angiotensin II type 1 receptor in radioligand binding assays and could reduce blood pressure significantly in spontaneously hypertensive rats(SHRs). From which, compound 2b displayed higher affinity binding to angiotensin II type 1 receptor at the same order of magnitude to irbesartan with an IC50 value of 1.26 ± 0.08 nM in radioligand binding assays. 2b showed an efficient and long-lasting effect in reducing blood pressure, the maximal reducing responses were 40.62 ± 4.08 mmHg of MBP at 15 mg/kg and 28.39 ± 2.09 mmHg at 10 mg/kg in SHRs, 39.56 ± 4.83 mmHg at 15 mg/kg and 29.05 ± 2.20 mmHg at 10 mg/kg in RHRs, the significant antihypertensive effect lasted beyond 12 h both in SHRs and in RHRs. In the single-dose pharmacokinetic experiments, compound 2b could be absorbed efficiently and metabolized smoothly in Wistar rats after oral administration. The values of Cmax, Tmax, AUC0-72 and MRT0-72 were 885.61 ± 432.7 ng/mL, 5.67 ± 1.51 h, 6110.28 ± 7398.33 ng/mL h and 7.87 ± 2.30 h at 10 mg/kg, 2945.55 ± 1543.67 ng/mL, 4.33 ± 0.82 h, 26473.62 ± 12217.16 ng/mL h and 10.24 ± 6.94 h at 15 mg/kg, 5759.03 ± 1331.75 ng/mL, 5 ± 1.10 h, 89488.44 ± 18413.15 ng/mL·h and 12.89 ± 2.0 h at 30 mg/kg respectively. The T1/2 values of the three groups were similar, about 9-10 h. Compound 2b was distributed into tissues rapidly and extensively after oral administration. The level of it was the highest in the liver, followed by in spleen, kidney, and the lowest in brain. The acute toxicity assays of 2b proved its low acute toxicity with an LD50 value of 1551.71 mg/kg, and no toxicity reaction appeared at dose of 1200.00 mg/kg. These encouraging results make compound 2b an effective, long-lasting and safe anti-hypertensive drug candidate and worthy of further investigation.

The design, synthesis, in vitro and in vivo evaluation of 6-substituted benzimidazole with 1, 4-disubsituted or 1, 5-disubsituted indole derivatives as novel angiotensin II receptor antagonists are outlined. Radioligand binding assays showed that several 6-substituted benzimidazole derivatives displayed high affinities binding to the angiotensin II type 1 receptor at the same order of magnitude to telmisartan. The biological evaluation on spontaneously hypertensive rats showed that 2-[4-[[2-n-propyl-4-methyl-6-(1-methylbenzimidazol-2-yl)benzimidazole-1-yl]methyl]-1H-indol-1-yl]benzoic acid, 1c, could cause significant decrease on MBP in a dose dependent manner. Its maximal response lowered 53 mmHg of MBP at 5 mg/kg and 64 mmHg of MBP at 10 mg/kg after oral administration, and the significant antihypertensive effect lasted beyond 24 h, which was better than both losartan and telmisartan. A study designed to determine acute toxicity showed that 1c had low acute toxicity with no significant changes in the weight and no obvious untoward reactions. The encouraging results make 1c an effective and durable anti-hypertension drug candidate and deserve further investigation for therapeutic application.

The development of novel photosensitizers is a challenging task for photodynamic therapy (PDT). Twelve novel photosensitizers (PSs), including porphins (P1-4), chlorins (C1-4) and bacteriochlorins (B1-4) were synthesized. The bacteriochlorins exhibited the longest absorption wavelength (λmax = 736 nm), which is higher than that of porphins (λmax = 630 nm) and chlorins (λmax = 644 nm). In vitro photodynamic activities on Eca-109 human esophageal carcinoma cells were evaluated by standard assays and all PSs showed photodynamic activity. Among them, B2 displayed the highest phototoxicity and the lowest dark toxicity. In addition, B2 exhibited best photodynamic antitumor efficacy on BALB/c nude mice bearing Eca-109 cells tumor. Therefore, B2 is a powerful and promising antitumor photosensitizer for PDT.

A series of new 6-substituted aminocarbonyl benzimidazole derivatives with 1, 4-disubsituted or 1, 5-disubsituted indole moiety and benzoic acid moiety were designed, synthesized and pharmacologically evaluated. Most of the synthesized compounds could bind to the AT1 receptor and decrease blood pressure significantly. Notably, 2e and 1h could obviously decrease MBP in a dose dependent manner. The maximal response lowered 57.9 ± 2.3 mmHg (2e) and 57.6 ± 1.9 mmHg (1h) of MBP at 10 mg/kg after oral administration, and the antihypertensive effect lasted beyond 24 h, which performed better than Losartan (Fig. 1). These results indicate that 2e and 1h are effective and long-lasting anti-hypertension drug candidates and deserve further investigation for therapeutic application.