Elucidation of flavonoids from potent Iranian Scutellaria species against Influenza A (H1N1) virus.

Objectives: Influenza A virus (IAV) is a contagious illness. Different species of Scutellaria genus are used as a traditional remedy to reduce influenza symptoms. This study aimed to investigate the anti-influenza capacity of several species of Iranian Scutellaria and identify active compounds of the most potent species for the first time. Materials and Methods: Some Iranian species of Scutellaria were collected from different regions of Iran, including S. pinnatifida with mucida, viridis, and alpina subspecies; S. tournefortii; S. tomentosa; S. persica. They were fractionated to chloroform and methanol. The total phenols and flavonoids of samples were examined by the folin-ciocalteau and aluminum-flavonoid complex methods, respectively. The 50% cytotoxic concentrations (CC50) on MDCK cells and non-cytotoxic concentrations (NCTC) were determined by MTT assay. The percentage of cell protection against IAV and their effect on virus titer were investigated in pre-, post-, and co-penetration treatment groups. Phytochemicals of the most effective species were isolated by various chromatographic methods and identified by different spectroscopic methods. Results: Methanol fraction of S. pinnatifida subsp. viridis demonstrated the highest amounts of flavonoid content and best activity against influenza A virus in all combination treatments, which reduced the virus titer by 5 logs with no cytotoxicity. Kaempferol-3-O-glucoside, quercetin-3-O-glucoside, apigenin-4'-methoxy-7-O-glucoside, luteolin, and luteolin-7-O-glucoside were purified and identified from this species. Conclusion: Scutellaria pinnatifida subsp. viridis can be introduced as a source of flavonoids with acceptable anti-influenza activity. S. tomentosa also showed potent antiviral effects and is a candidate for elucidation in further studies.

Development of a Radiolabeled Amlodipine Analog for L-type Calcium Channel Imaging.

PURPOSE: The non-invasive imaging and quantification of L-type calcium channels (also known as dihydropyridine channels) in living tissues is of great interest in diagnosis of congestive heart failure, myocardial hypertrophy, irritable bowel syndrome etc. METHODS: Technetium-99m labeled amlodipine conjugate ([99mTc]-DTPA-AMLO) was prepared starting freshly eluted (<1 h) 99mTechnetium pertechnetate (86.5 MBq) and conjugated DTPAAMLO at pH 5 in 30 min at room temperature in high radiochemical purity (>99%, RTLC; specific activity: 55-60 GBq/mmol). The calcium channel blockade activity (CCBA) and apoptosis/necrosis assay of DTPA-amlodipine conjugate evaluations were performed for the conjugate. Log P, stability, bio-distribution and imaging studies were performed for the tracer followed by biodistribution studies as well as imaging. RESULTS: The conjugate demonstrated low toxicity on MCF-7 cells and CCBA (at µm level) compared to the amlodipine. The tracer was stable up to 4 h in final production and presence of human serum and log P (-0.49) was consistent with a water soluble complex. The tracer was excreted through kidneys and liver as expected for dihydropyridines; excluding excretory organs, calcium channel rich smooth muscle cells; including colon, intestine and lungs which demonstrated significant uptake. SPECT images supported the bio-distribution data up to 4 h. CONCLUSION: significant uptake of [99mTc]-DTPA-AMLO was obtained in calcium channel rich organs. The complex can be a candidate for further SPECT imaging for L-type calcium channels.

Preparation and preclinical evaluation of 68Ga-DOTA-amlodipine for L-type calcium channel imaging.

AIM: In order to develop a possible tracer for L-type calcium channel imaging, we here report the development of a Ga-68 amlodipine derivative for possible PET imaging. MATERIALS AND METHODS: Amlodipine DOTA conjugate was synthesized, characterized and went through calcium channel blockade, toxicity, apoptosis/necrosis tests. [68Ga] DOTA AMLO was prepared at optimized conditions followed by stability tests, partition coefficient determination and biodistribution studies using tissue counting and co incidence imaging up to 2 h. RESULTS: [68Ga] DOTA AMLO was prepared at pH 4-5 in 7-10 min at 95°C in high radiochemical purity (>99%, radio thin layer chromatography; specific activity: 1.9-2.1 GBq/mmol) and was stable up to 4 h with a log P of -0.94. Calcium channel rich tissues including myocardium, and tissues with smooth muscle cells such as colon, intestine, and lungs demonstrated significant uptake. Co incidence images supported the biodistribution data up to 2 h. CONCLUSIONS: The complex can be a candidate for further positron emission tomography imaging for L type calcium channels.