Rapid synthesis of maleimide functionalized fluorine‐18 labeled prosthetic group using “radio‐fluorination on the Sep‐Pak” method

Following our recently published fluorine‐18 labeling method, “Radio‐fluorination on the Sep‐Pak”, we have successfully synthesized 6‐[¹⁸F]fluoronicotinaldehyde by passing a solution (1:4 acetonitrile: t‐butanol) of its quaternary ammonium salt precursor, 6‐(N,N,N‐trimethylamino)nicotinaldehyde trifluoromethanesulfonate ( 2 ), through a fluorine‐18 containing anion exchange cartridge (PS‐HCO₃). Over 80% radiochemical conversion was observed using 10 mg of precursor within 1 minute. The [¹⁸F]fluoronicotinaldehyde ([¹⁸F] 5 ) was then conjugated with 1‐(6‐(aminooxy)hexyl)‐1H‐pyrrole‐2,5‐dione to prepare the fluorine‐18 labeled maleimide functionalized prosthetic group, 6‐[¹⁸F]fluoronicotinaldehyde O‐(6‐(2,5‐dioxo‐2,5‐dihydro‐1H‐pyrrol‐1‐yl)hexyl) oxime, 6‐[¹⁸F]FPyMHO ([¹⁸F] 6 ). The current Sep‐Pak method not only improves the overall radiochemical yield (50 ± 9%, decay‐corrected, n = 9) but also significantly reduces the synthesis time (from 60‐90 minutes to 30 minutes) when compared with literature methods for the synthesis of similar prosthetic groups.     

Development and Validation of Stability-indicating HPLC Method for Simultaneous Estimation of Cefixime and Linezolid

A stability-indicating reverse phase high performance liquid chromatography method was developed and validated for cefixime and linezolid. The wavelength selected for quantitation was 276 nm. The method has been validated for linearity, accuracy, precision, robustness, limit of detection and limit of quantitation. Linearity was observed in the concentration range of 2-12 μg/ml for cefixime and 6-36 μg/ml for linezolid. For RP-HPLC, the separation was achieved by Phenomenex Luna C₁₈ (250×4.6 mm) 5 μm column using phosphate buffer (pH 7):methanol (60:40 v/v) as mobile phase with flow rate 1 ml/min. The retention time of cefixime and linezolid were found to be 3.127 min and 11.986 min, respectively. During force degradation, drug product was exposed to hydrolysis (acid and base hydrolysis), H₂O₂, thermal degradation and photo degradation. The % degradation was found to be 10 to 20% for both cefixime and linezolid in the given condition. The method specifically estimates both the drugs in presence of all the degradants generated during forced degradation study. The developed methods were simple, specific and economic, which can be used for simultaneous estimation of cefixime and linezolid in tablet dosage form.     

Ichthyosiform Large Plaque Parapsoriasis: Report of a Rare Entity

Large plaque parapsoriasis (LPP) is an idiopathic, chronic scaly dermatosis classified within parapsoriasis group of diseases, occurring commonly in middle aged patients of all races and geographic regions. LPP and its variants are closely related to the patch stage of mycosis fungoides. The two types of LPP mostly described are the poikilodermatous and retiform parapsoriasis. We are reporting an ichthyosiform LPP for its rarity.     

Endothelin receptor antagonists--an overview

In thirteen years since the appearance of Endothelin (ET) on the international scene, possibility of its involvement in a variety of diseases has attracted the attention of medicinal chemists in search of novel therapeutics for various cardiovascular diseases (CVDs). Discovery of pharmaceutical agents which either block the generation of ET from its precursor or antagonize its binding to cellular receptor, should not only provide means to assess the physiological role of ET, but lead to useful therapy for conditions associated with altered production or responsiveness to ET. In this review article, we have attempted to present in a classified format, the kaleidoscope of ET receptor antagonists that have emerged through structure activity relationship studies using the parent peptide as well as from screening of various compound libraries. By all indications, the variety and range of small molecules that are currently under investigation continues to open up newer opportunities and lures fresh groups of scientists into this research arena. Presently a number of these compounds are in the clinics, being evaluated for their beneficial effects in a range of human pathologies such as essential hypertension and chronic heart failure.     

Effects of Aniline–An Aromatic Amine to Some Freshwater Organisms

We determined the acute and chronic toxicity of aniline to tilapia (Oreochromis mossambicus), cladoceran crusatcea (Moina micrura) and oligochaete worm (Branchiura sowerbyi) using static bioassay tests. The 96h LC₅₀ values of aniline for O. mossambicus, M. micrura and B. sowerbyi were 69.4, 0.6 and 586mg l^–1 respectively. Tilapia responded to even low concentrations of aniline: the fish lost appetite at aniline concentrations as low as 0.02mg l^–1. A 90 d outdoor bioassay with tilapia showed that 0.02mg l^–1 aniline reduced fish yield, specific growth rate and food conversion efficiency. Reproductive functions of fish were affected by aniline at a concentration of 0.5mg l^–1 and above. Dissolved oxygen, primary productivity and plankton population of the test medium also were significantly reduced at 2.65 and 6.94mg l^–1 aniline.     

A first synthesis of 18F‐radiolabeled lapatinib: a potential tracer for positron emission tomographic imaging of ErbB1/ErbB2 tyrosine kinase activity

Fluorine‐18‐labeled lapatinib has been successfully synthesized for the first time by the reaction of a dimethylformamide solution of meta‐[¹⁸F]fluorobenzylbromide with a Boc‐protected lapatinib precursor fragment. The reaction proceeded in the presence of K₂CO₃ at 110 °C for 10 min in a microwave and was followed by Boc‐group deprotection with trifluoroacetic acid. The overall radiochemical yield of the reaction starting from the radiofluorination of the iodonium salt was 8–12% (uncorrected, n = 6) in a 140‐min synthesis time.     

Collagen scaffolds derived from fresh water fish origin and their biocompatibility

Collagen, a major component of native extracellular matrix, has diverse biomedical applications. However, its application is limited due to lack of cost-effective production and risk of disease transmission from bovine sources currently utilized. This study describes fabrication and characterization of nano/micro fibrous scaffolds utilizing collagen extracted from fresh water fish origin. This is the first time collagen extracted from fresh water fish origin was studied for their biocompatibility and immunogenicity. The nano/micro fibrous collagen scaffolds were fabricated through self-assembly owing to its amphiphilic nature and were subsequently cross-linked. In vitro degradation study revealed higher stability of the cross-linked scaffolds with only ~50% reduction of mass in 30 days, while the uncross-linked one degraded completely in 4 days. Further, minimal inflammatory response was observed when collagen solution was injected in mice with or without adjuvant, without significant dilution of sera. The fish collagen scaffolds exhibited considerable cell viability and were comparable with that of bovine collagen. SEM and fluorescence microscopic analysis revealed significant proliferation rate of cells on the scaffolds and within 5 days the cells were fully confluent. These findings indicated that fish collagen scaffolds derived from fresh water origin were highly biocompatible in nature.