A review: FDA-approved fluorine-containing small molecules from 2015 to 2022.

Fluorine-containing small molecules have occupied a special position in drug discovery research. The successful clinical use of fluorinated corticosteroids in the 1950s and fluoroquinolones in the 1980s led to an ever-increasing number of approved fluorinated compounds over the last 50 years. They have shown various biological properties such as antitumor, antimicrobial, and anti-inflammatory activities. Fluoro-pharmaceuticals have been considered a strong and practical tool in the rational drug design approach due to their benefits from potency and ADME (absorption, distribution, metabolism, and excretion) points of view. Herein, approved fluorinated drugs from 2015 to 2022 were reviewed.

Design, synthesis, spectroscopic characterization, in vitro tyrosinase inhibition, antioxidant evaluation, in silico and kinetic studies of substituted indole-carbohydrazides.

In the current study, twenty-five indole-carbohydrazide derivatives linked to different aryl substitutions were rationally designed and synthesized. The structures of all derivatives were confirmed using different spectroscopic techniques including 1H NMR, 13C NMR, Mass spectrometry, and elemental analysis. The tyrosinase inhibitory activities of all synthetic compounds exhibited IC50 values in the range of 0.070 to > 100 µM. Structure-activity relationships showed that compounds 4f (R = 4-OH, IC50 = 0.070 µM), 8f (R = 4-OH, IC50 = 0.072 µM), and 19e (IC50 = 0.19 µM) with para-OH substituent at the R position was found to be the most active members of all three tested series. Kinetic studies exhibited that compounds 4f, 8f, and 19e are mixed-type inhibitors. Furthermore, toxicity and cell-based anti-melanogenesis assessments were performed on the most potent derivatives and it was shown that 4f, 8f, and 19e had no toxicity at 8 µM and reduced the percent of melanin content to 68.43, 72.61, 73.47 at 8 µM, respectively. In silico analyses of absorption, distribution, metabolism, and excretion (ADME) profile of synthesized compounds showed that these molecules followed drug-likeness rules and acceptable predictive ADMET features. Results of the docking study were almost in line with biological results with ChemPLP values of 53.56 to 79.33. Also, the docking study showed the critical interactions of potent inhibitors with the active site of the enzyme which affects the potency of the synthesized hybrids. Based on molecular dynamic simulations, compound 4f exhibited pronounced interaction with the critical residues of the tyrosinase active site so that the indole ring participated in H-bond interaction with Gly281 and 4-hydroxy benzylidene recorded another H-bond interaction with Asp289 plus hydrophobic interactions with Phe292. Hydrazide linker also exhibited three H-bond interactions with His263 and Gly281.

Diagnostic Value and Effective Factors on Transbronchial Lung Biopsy Using Cup and Alligator Forceps.

BACKGROUND: Lung biopsy through the airways by using a flexible bronchoscope (transbronchial lung biopsy: TBLB) is a suitable method for obtaining tissue specimens. This study aimed at evaluating the factors influencing TBLB results in order to increase the diagnostic power of this method. MATERIALS AND METHODS: This was a prospective double blind observational study. We had a total of 44 patients with pulmonary lesions who underwent biopsy and 4 specimens were obtained from each patient. A total of 176 specimens were obtained from all patients. Biopsy specimens were taken using cup and alligator forceps alternatively. Characteristics of the obtained specimens including size, floatation, alveolarity, and bleeding were thoroughly studied. After sending to the pathologist, specimens were divided into 2 groups of diagnostic and non-diagnostic specimens. RESULTS: Of a total of 176 specimens, 37 (21%) were diagnostic and 139 (79%) were non-diagnostic. From 88 specimens obtained by the alligator forceps, 16 were diagnostic while from the same number of specimens taken by the cup forceps 21 had diagnostic value. However, this difference was not statistically significant (P>0.05). Of the small specimens (57 cases), 12 (21.1%) were diagnostic while among the 66 medium specimens, 12 (18.2%) and from the 53 large specimens, 13 (24.5%) were diagnostic. No statistically significant difference was detected in this respect (P>0.05). Among specimens floating on the surface of the liquid (48 cases), 6 (12.5%) had diagnostic value. Of the 12 specimens suspended in the liquid, 2 (16.7%) and among the 116 specimens precipitated at the bottom, 29 (25%) were diagnostic. These differences were not significant either (P>0.05). Of the 84 specimens with more than 20 alveoli, 31 (36.9%) were diagnostic. Among 26 specimens with less than 20 alveoli 5 (19.2%) were diagnostic. This correlation was statistically significant indicating that the higher the number of alveoli in the biopsy specimen, the greater the chance of being diagnostic. CONCLUSION: This study failed to find a significant correlation between the diagnostic power of TBLB and type of forceps, sample size or floatation of the specimen in the liquid. However, number of alveoli present in the tissue specimens was significantly correlated with its diagnostic value. Increasing the number of specimens to four can increase the chance of diagnosis.

Balloon bronchoplasty: case series.

Central airway stenosis may be a manifestation of benign or malignant lesions and can be a life threatening condition. There are different surgical and endoscopic modalities for treatment of these lesions. Balloon bronchoscopy is an interventional pulmonologic modality and can be performed under direct vision or fluoroscopic guidance. This technique can be used along with other interventional modalities for treatment of patients with tracheal stenosis. In this study we report balloon bronchoscopy as an interventional modality in a series of patients with tracheal stenosis and assess the outcome.

Diagnostic Yield of Transbronchial Needle Aspiration (TBNA) for Cases with Intra-Thoracic Lymphadenopathies.

BACKGROUND: Evaluation of the lymph nodes in cases with lung cancer for diagnosis or staging has been considered since many years ago. Various methods have been developed for obtaining a sample from lymph nodes. This study was conducted in a research institute with high patient turnover and aimed at evaluating the diagnostic yield of TBNA and effective factors on diagnosis and related complications in patients with pulmonary lesions. MATERIALS AND METHODS: Our understudy population included all patients suffering from undiagnosed intrathoracic lymphadenopathies with no accompanying pulmonary lesions on chest CT scan who had been hospitalized in Masih Daneshvari Hospital or referred to its bronchoscopy unit. After determining the anatomic location of lymphadenopathy (LAP), patients underwent fiberoptic bronchoscopy (FOB) and TBNA using 19-gauge eXcelon aspiration needle. Four samples were taken from each patient from the same LAP location. In this study, 39 patients were evaluated. RESULTS: The most common anatomic location of lymph node involvement among our understudy patients was the paratracheal area which was involved in 14 (45.2%) patients followed by subcarinal area in 12 cases (38.7%) and hilar involvement also in 12 cases (38.7%). Five patients (15.6%) had lymphadenopathies in other anatomical locations. Evaluation of the aspirates obtained by TBNA showed that the sample was adequate and diagnostic in 21 patients (55.26%), adequate but non-diagnostic in 9 patients (23.68%) and inadequate in 8 cases (21.06%). Definite diagnosis was made in 22 patients among which the most common diagnosis was atypical and malignant lesions in 11 cases (50%) followed by sarcoidosis in 8 (36.36%), tuberculosis (TB) in 2 (9.09%) and other diagnoses in 1 (4.55%) case. CONCLUSION: Based on our study results, TBNA was diagnostic in more than half the cases. Various studies have reported a wide range of results in this respect but all of them including ours emphasize on the acceptable diagnostic yield of this technique.