Sustainable Synthesis of Guanidine Derivatives and Computational Assessment of their Antidiabetic Efficacy.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) represents a significant and pressing worldwide health concern, necessitating the quest for enhanced antidiabetic pharmaceuticals. Guanidine derivatives, notably metformin and buformin, have emerged as pivotal therapeutic agents for T2DM management. AIMS: The present study introduces an efficient one-pot synthesis method for the production of symmetrical guanidine compounds. METHODS: This synthesis involves the reaction of isothiocyanates with secondary amines, employing an environmentally friendly and recyclable reagent, tetrabutylphosphonium tribromide (TBPTB). RESULTS: A comprehensive assessment of the biological activity of the synthesized guanidine compounds, specifically in the context of T2DM, has been rigorously conducted. CONCLUSION: Additionally, computational analyses have unveiled their substantial potential as promising antidiabetic agents. Results highlight the relevance of these compounds in the ongoing pursuit of novel therapeutic solutions for T2DM.

Avascular Necrosis of Femur as a Complication of Cushing's Syndrome Due to Adrenocortical Carcinoma.

A wide range of clinical presentations for Cushing's syndrome has been described in the literature. Avascular necrosis of femur is a well-recognized complication of excessive glucocorticoid administration, but its occurrence due to endogenous hypercortisolism is rare. We present the case of a 47-year-old male who presented to us with severe low backache, hypertension, uncontrolled diabetes, and other signs and symptoms of Cushing's syndrome. Hormonal evaluation confirmed hypercortisolism, and a contrast-enhanced computed tomography of the abdomen localized the lesion in the left adrenal gland. Assessment of the severe low back ache-the main symptom for which the patient came to us-by magnetic resonance imaging of the spine and pelvis revealed avascular necrosis of bilateral femoral heads. Resection of the left adrenal gland revealed an adrenocortical carcinoma. To the best of our knowledge, this is only the second case where an adrenocortical cancer leading to hypercortisolism is the cause of avascular necrosis of hip.

OTOPLAN-Based Study of Intracochlear Electrode Position Through Cochleostomy and Round Window in Transcanal Veria Technique.

To study the postoperative visualisation of the electrode array insertion angle through transcanal Veria approach in both round window and cochleostomy techniques. Retrospective study. Tertiary care centre. 26 subjects aged 2-15 years implanted with a MED-EL STANDARD electrode array (31.5 mm) through Veria technique were selected. 16 had the electrode insertion through the round window, 10 through anteroinferior cochleostomy. DICOM files of postoperative computer tomography (CT) scans were collected and analysed using the OTOPLAN 3.0 software. Examined parameters were cochlear duct length, average angle of insertion depth. Pearson's Correlation Test was utilized for statistical analysis. Average cochlear duct length was 38.12 mm, ranging from 34.2 to 43 mm. Average angle of insertion depth was 666 degrees through round window insertion and 670 degrees through cochleostomy insertion. Pearson's correlation showed no significant difference in average angle of insertion depth between subjects with cochleostomy and round window insertion. Detailed study on the OTOPLAN software has established that there remains no difference between round window insertion or cochleostomy insertion when it comes to electrode array position and placement in the scala tympani. It is feasible to perform round window insertion and cochleostomy insertion through transcanal Veria approach as this technique provides good visualisation. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03228-5.

Synthesis, In Vitro Evaluation, Molecular Docking and DFT Studies of Some Phenyl Isothiocyanates as Anticancer Agents.

BACKGROUND: Isothiocyanates (ITCs) are small molecules that are important in synthetic organic chemistry, but their actual importance lies in their potential as anti-carcinogens. Through this piece of work, an effort was made to assess the anti-cancer activity of some simple ITCs which can be synthesized through easy greener pathways. METHODS: Cell proliferation assay was performed on ovarian cancer cells (PA-1) and non-tumorigenic ovarian epithelial cells (IOSE-364). Furthermore, qRT-PCR for transcript expression levels of Spindlin1 and caspases in ovarian cancer cells and cell cycle analysis was performed. In silico studies were incorporated to understand the mode of ligand-protein interaction, ADME/Toxicity and drug-likeliness parameters. Density functional theory studies have been also been employed on the ITCs to assess their efficiency in anticancer activity. RESULTS: An inexpensive, environmentally benign pathway has been developed for synthesizing a series of ITCs. Among the synthesized ITCs, NC6 showed better cytotoxic effects as compared to its counterparts. Novel findings revealed that NC6 had 5-folds lower transcript expression levels of Spindlin1 and induced caspases 3 and 7 expressions assessed by qRT-PCR in ovarian cancer cells. Furthermore, flow cytometry assay showed the cell cycle arrest at G1/S phase of cell cycle. The molecular docking studies revealed favorable binding affinities and the physiochemical parameters were predicted to be compatible with drug-likeliness. CONCLUSION: The results demonstrated the possibility that small isothiocyanate molecules which can be synthesized by a simple green methodology, can pose as promising candidates for their application as anticancer agents.

Green Synthesis of Bromo Organic Molecules and Investigations on Their Antibacterial Properties: An Experimental and Computational Approach.

A simple, environmentally benign methodology has been developed to synthesize some bromoorganic compounds which have potential as antimicrobial agents. The required compounds were obtained through microwave (MW) irradiation, on-water reactions and using cetyltrimethylammonium tribromide (CTMATB) as the bromine source. The high yield of the product could be achieved within short reaction times, thus representing the main attribute of the present synthetic approach. The compounds were evaluated for in vitro antibacterial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Bacillus subtilis. Further, in silico studies were carried out to elucidate the interactions of the compounds with the bacterial proteins.

A Novel One-pot Synthesis of Isothiocyanates and Cyanamides from Dithiocarbamate Salts Using Environmentally Benign Reagent Tetrapropylammonium Tribromide.

A highly efficient and simple protocol for the synthesis of isothiocyanates and cyanamides from their respective amines in the presence of a mild, efficient, and non-toxic reagent tetrapropylammonium tribromide is described. High environmental acceptability of the reagents, cost effectiveness and high yields are the important attributes of this methodology.