Cationic Porphyrin-Based Ionic Nanomedicines for Improved Photodynamic Therapy.

This study presents the synthesis and characterization of monosubstituted cationic porphyrin as a photodynamic therapeutic agent. Cationic porphyrin was converted into ionic materials by using a single-step ion exchange reaction. The small iodide counteranion was replaced with bulky BETI and IR783 anions to reduce aggregation and enhance the photodynamic effect of porphyrin. Carrier-free ionic nanomedicines were then prepared by using the reprecipitation method. The photophysical characterization of parent porphyrin, ionic materials, and ionic nanomaterials, including absorbance, fluorescence and phosphorescence emission, quantum yield, radiative and nonradiative rate, and lifetimes, was performed. The results revealed that the counteranion significantly affects the photophysical properties of porphyrin. The ionic nanomaterials exhibited an increase in the reactive oxygen yield and enhanced cytotoxicity toward the MCF-7 cancer cell line. Examination of results revealed that the ionic materials exhibited an enhanced photodynamic therapeutic activity with a low IC50 value (nanomolar) in cancerous cells. These nanomedicines were mainly localized in the mitochondria. The improved light cytotoxicity is attributed to the enhanced photophysical properties and positive surface charge of the ionic nanomedicines that facilitate efficient cellular uptake. These results demonstrate that ionic material-based nanodrugs are promising photosensitizers for photodynamic therapy.

Design, Synthesis and Pharmacological Evaluation of Gastro- Protective Anti-inflammatory Analgesic Agents based on Dual Oxidative Stress / Cyclooxygenase Inhibition.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) derived local generation of reactive oxygen species (ROS) plays a crucial role in the formation of gastric ulceration. OBJECTIVE: Therefore, anti-inflammatory analgesics with potent antioxidant activity could be a potential therapeutic strategy for the treatment of pain and inflammatory disorders without gastrointestinal (GI) side effects. METHODS: In an effort to develop gastroprotective analgesic and anti-inflammatory agents, a series of 2-methylamino-substituted-1H-benzo[d] imidazol-1-yl) (phenyl) methanone derivatives were synthesized and evaluated in vitro for cyclooxygenase (COX) inhibition as well as anti-oxidant potential by the FRAP assay. The compounds with significant in vitro COX-1/COX-2 inhibitory activity and antioxidant activity were further screened in vivo for their anti-inflammatory and analgesic activities. Moreover, the ulcerogenic potential of test compounds was also studied. To gain insight into the plausible mode of interaction of compounds within the active sites of COX-1 and COX-2, molecular docking simulations were performed. RESULTS: Among the various synthesized molecules, most of the compounds showed good cyclooxygenase inhibitory activity and efficient antioxidant activity in FRAP assay. After preliminary and indicative in vitro assays, three compounds exhibited most significant antiinflammatory and analgesic activity with better gastric tolerability during their in vivo evaluation. Ligand interaction studies indicated highest dock score -43.05 of 1,2- disubstituted benzimidazole derivatives in comparison to the reference ligand -30.70. Overall studies provided us (2-((4-methoxyphenylamino) methyl) -1h-benzo [d] imidazol- 1-yl) (phenyl) methanone as a lead with potent gastro-protective anti-inflammatory and analgesic activities that can be used for future research. CONCLUSION: From the above results, it can be concluded that designing of multifunctional molecules with COX-1/COX-2 inhibitory and anti-oxidant activities could hold a great promise for further development of GI-safer NSAIDs.

Benzimidazole: an emerging scaffold for analgesic and anti-inflammatory agents.

Within the vast range of heterocycles, benzimidazole and its derivatives are found to be trendy structures employed for discovery of drugs in the field of pharmaceutical and medicinal chemistry. The unique structural features of benzimidazole and a wide range of biological activities of its derivatives made it privileged structure in drug discovery. Recently, benzimidazole scaffold has emerged as a pharmacophore of choice for designing analgesic and anti-inflammatory agents active on different clinically approved targets. To pave the way for future research, there is a need to collect the latest information in this promising area. In the present review we have collated published reports on this versatile core to provide an insight so that its full therapeutic potential can be utilized for the treatment of pain and inflammation.

Galactomannan gum coated mucoadhesive microspheres of glipizide for treatment of type 2 diabetes mellitus: In vitro and in vivo evaluation.

Type 2 diabetes mellitus is a heterogeneous disease of polygenic origin and involves both defective insulin secretion and peripheral insulin resistance. Studies have shown that post-meal hyperglycemic spikes are associated with increased cardiovascular mortality in type 2 diabetes. Over the past decade, a major interest in control of postprandial glucose excursion has emerged and a plethora of new medications that specifically target postprandial hyperglycemia were discovered. Despite the availability of new agents for treatment of type 2 diabetes mellitus, oral sulfonylureas remain a cornerstone of therapy, because they are relatively inexpensive and are well tolerated. However, hypoglycemia is a major safety concern with sulfonylureas and it is one major risk factor requiring hospitalization. Glipizide is a potent, rapid-acting with short duration of action and well tolerated second-generation sulfonylurea effective in reducing postprandial glucose levels. However, risk of postprandial hypoglycemia and post-meal glucose excursions, if dose missed before meal; are always associated with the use of glipizide for treatment of type 2 diabetes mellitus. Since, the site of absorption of glipizide is from stomach thus dosage forms that are retained in stomach by mucoadhesion; would increase absorption, improve drug efficiency and decrease dose requirements. Microsphere carrier systems made by using polymer galactomannan having strong mucoadhesive properties and easily biodegradable could be an attractive strategy to formulate. The purpose of this research work is to formulate galactomannan coated mucoadhesive microspheres of glipizide and systematically evaluate its in vitro characteristics and in vivo performance for sustained glucose lowering effect and improvement in diabetic condition as compared to immediate release of glipizide.

Synthesis and pharmacological evaluation of novel 5-substituted-1-(phenylsulfonyl)-2-methylbenzimidazole derivatives as anti-inflammatory and analgesic agents.

A series of novel 5-substituted-1-(phenylsulfonyl)-2-methylbenzimidazole derivatives have been synthesized. The structures of these compounds were established by IR, 1H NMR, 13C NMR, Mass spectral data and elemental analyses. Compounds were evaluated for their anti-inflammatory and analgesic activity as well as gastric ulcerogenic effects. Derivatives 4a, 4b and 4c exhibited moderate to good anti-inflammatory and analgesic activity in carrageenan-induced rat paw edema and acetic acid-induced writhing in mice, respectively, with low ulcerogenicity compared with the standard drug indomethacin.