Tris(boranil) Columnar Liquid Crystalline Fluorophores: pseudo-Triphenylene Boron(III) Complexes with Peripheral N-B-O Linkages.

The borate complexes derived from salicylaldimine ligands, called boranils, possess a wide range of photophysical and electronic characteristics intrinsically. The unique combination of molecular rigidity, rendered by four-coordinate boron bridges, and extended π-conjugation enable them to serve as technically feasible fluorescent materials (dyes). The incorporation of liquid crystallinity in these boron(III) complexes, especially the columnar (Col) mesomorphism, which is overlooked hitherto, would provide a new dimension to these complexes. Herein, we report the first examples of tris(boranil) discotic liquid crystal (LC) dyes that have been readily synthesized by treating tris(N-salicylideneaniline)s, (TSAN)s, with BF3 .Et2 O in the presence of an acid quencher. These C3 -symmetric borate complexes self-assemble into the Col phase, existing over a wide thermal span including room temperature. The 2D periodic order of the Col phases shows dependence on the length of the peripheral tails. The photophysical measurements reveal the fluorescence emission in their two condensed states viz., solid and Col phase, and in solution. Their electrochemical, two-step oxidation process coupled with the aforesaid features upholds their significance in applied research.

ZY12201, A Potent TGR5 Agonist: Identification of a Novel Pan CYP450 Inhibitor Tool Compound for In-Vitro Assessment.

BACKGROUND: Identification of clinical drug-drug interaction (DDI) risk is an important aspect of drug discovery and development owing to poly-pharmacy in present-day clinical therapy. Drug metabolizing enzymes (DME) plays important role in the efficacy and safety of drug candidates. Hence evaluation of a New Chemical Entity (NCE) as a victim or perpetrator is very crucial for DDI risk mitigation. ZY12201 (2-((2-(4-(1H-imidazol-1-yl) phenoxy) ethyl) thio)-5-(2-(3, 4- dimethoxy phenyl) propane-2-yl)-1-(4-fluorophenyl)-1H-imidazole) is a novel and potent Takeda-G-protein-receptor-5 (TGR-5) agonist. ZY12201 was evaluated in-vitro to investigate the DDI liabilities. OBJECTIVE: The key objective was to evaluate the CYP inhibition potential of ZY12201 for an opportunity to use it as a tool compound for pan CYP inhibition activities. METHOD: In-vitro drug metabolizing enzymes (DME) inhibition potential of ZY12201 was evaluated against major CYP isoforms (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4/5), aldehyde oxidase (AO), monoamine oxidase (MAO), and flavin-containing monooxygenase (FMO in human liver cytosol/mitochondrial preparation/ microsomes using probe substrates and Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) method. RESULTS: The study conducted on ZY12201 at 100 µM ZY12201 was found to reduce the metabolism of vanillin (AO probe substrate), tryptamine (MAO probe substrate), and benzydamine (FMO probe substrate) by 49.2%, 14.7%, and 34.9%, respectively. ZY12201 Ki values were 0.38, 0.25, 0.07, 0.01, 0.06, 0.02, 7.13, 0.03 and 0.003 µM for CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5 (substrate: testosterone) and CYP3A4/5 (substrate: midazolam), respectively. Time-dependant CYP inhibition potential of ZY12201 was assessed against CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4/5 and no apparent IC50 shift was observed. CONCLUSIONS: ZY12201, at 100 µM concentration showed low inhibition potential of AO, MAO, and FMO. ZY12201 was found as a potent inhibitor of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4/5 while moderately inhibits to CYP2E1. Inhibition of CYP1A2, CYP2B6, CYP2C19, and CYP2E1 by ZY12201 was competitive, while inhibition of CYP2C8, CYP2C9, CYP2D6, and CYP3A4/5 was of mixed-mode. ZY12201 is a non-time-dependent inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5. In summary, the reported Ki values unequivocally support that ZY12201 has a high potential to inhibit all major CYP isoforms. ZY12201 can be effectively used as a tool compound for in-vitro evaluation of CYP-based metabolic contribution to total drug clearance in the lead optimization stage of Drug Discovery Research.

Role of Laparoscopy in Chronic and Recurrent Abdominal Pain-Rural Area Experience.

Chronic and recurrent abdominal pain is a common problem faced by the medical specialist. It leads to physical and psychological disability in a person. Despite radiological and clinical investigations when diagnosis cannot be ascertained then laparoscopy is one of the modalities that could be of benefit. We aim to evaluate the diagnostic and therapeutic value of laparoscopy in cases with chronic abdominal pain. Sixty-seven patients who attended the outpatient department of MGIMS, Sewagram with chronic and recurrent abdominal pain were included in this prospective study. All patients underwent preoperative workup and were subjected to laparoscopic evaluation. The commonest site of pain was the periumbilical region and nausea was the most common accompanying clinical feature. Adhesions were the most common laparoscopic findings (48.3 %) followed by appendiceal pathology (14.6 %). Abdominal Kochs which is predominant in developing countries was seen in 11.4 % of the cases. Laparoscopy is an effective diagnostic and therapeutic modality in the management of patients with chronic abdominal pain.

Delayed presentation of port-site metastasis from an unknown gastrointestinal malignancy following laparoscopic cholecystectomy.

Port-site metastasis (PSM) is often encountered during laparoscopic surgery in patients with malignancy. We report a 45-year-old woman who presented with a single PSM from papillary adenocarcinoma after undergoing laparoscopic cholecystectomy for calculus cholecystitis. Post cholecystectomy, a diagnosis of chronic cholecystitis was confirmed on histopathology. The patient presented with a mass at the site of epigastric port 28 months after surgery. PSM was suspected on clinical examination, which was supported by findings on computed tomography and further confirmed by fine-needle aspiration cytology of the lump. The patient underwent surgical clearance of the mass, and histopathological examination proved the lesion to be papillary adenocarcinoma. The site of the primary tumour was not detected even after thorough examination. Based on the histopathology report following local surgical clearance, the patient was started on chemotherapy. This case is unusual because of the long delay prior to the presentation of PSM and the unknown primary malignancy.