Exploration of oxadiazole clubbed benzhydrylpiperazine pharmacophoric features as structural feature for antidepressant activity: In vitro, in vivo and in silico analysis.

Arylpiperazine clubbed various heterocyclic molecules present potential pharmacophoric structural features for the development of psychoactive drugs. There are various CNS active molecules possessing arylpiperazine moiety in their pharmacophore approved by USFDA. In the current study, we have explored the benzhydrylpiperazine moiety clubbed with various substituted oxadiazole moieties (AP1-12) for their monoamine oxidase (MAO) inhibition and antidepressant potential. Compounds AP3 and AP12 exhibited highly potent and selective MAO-A inhibition with IC50 values of 1.34 ± 0.93 µM and 1.13 ± 0.54 µM, respectively, and a selectivity index of 10- and 13-folds, respectively. Both the compounds displayed reversible binding character at the active site of MAO-A. In further in vivo evaluation, both the compounds AP3 and AP12 displayed potential antidepressant-like character in FST and TST studies via significantly reduced immobility time in comparison to non-treated animals. These compounds displayed no cytotoxicity in SH-SY5Y cell lines, which indicates that these compounds are safe for further evaluation. In silico studies reveal that synthesized compounds possess drug-likeness with minimal to no toxicity. In silico studies were conducted to understand the binding interactions and stability of compounds at the binding pocket of enzyme and observed that both the best compounds fit well at the active site of MAO-A lined by amino acid residues Tyr69, Asn181, Phe208, Ile335, Leu337, Phe352, and Tyr444 similar to standard MAO-A inhibitor clorgiline. The molecular dynamic studies demonstrated that AP3 and AP12 formed quite a stable complex at the active site of MAO-A and did not break under small abruption forces. The favourable binding interactions and appropriate ADMET properties present the benzhydrylpiperazine clubbed oxadiazole pharmacophoric features as a potential structural skeleton for further clinical evaluation and development of a new antidepressant drug molecule.

Synthesis of Alkyl and Aryl Boronate Esters via CeO2-Catalyzed Borylation of Alkyl and Aryl Electrophiles Including Alkyl Chlorides.

A recyclable protocol using a CeO2-nanorod catalyst for borylation of alkyl halides with B2pin2 (pin = OCMe2CMe2O) is reported. A wide range of synthetically useful alkyl boronate esters are readily obtained from primary and secondary alkyl electrophiles, including unactivated alkyl chlorides, demonstrating broad utility and functional group tolerance. Preliminary investigation revealed an involvement of in situ formed catalytically active boryl species. The catalyst can be reused for up to six runs without appreciable loss in activity. In addition, we have demonstrated the use of this recyclable catalyst for the borylation of aryl halides with B2pin2, providing valuable aryl boronate esters under neat conditions.

Transition metal- and solvent-free anti-Markovnikov selective protoboration of alkenes with bis(pinacolato)diboron.

An efficient anti-Markovnikov selective transition metal- and solvent-free Lewis base-mediated protoboration of aromatic and aliphatic alkenes with bis(pinacolato)diboron (B2pin2) as the boron reagent is reported. This protocol is practical and demonstrates broad substrate scope and good functional-group tolerance on alkenes to give synthetically useful alkyl boronate esters in excellent yields under mild reaction conditions. The gram-scale reaction further highlighted the usefulness of this method.

SMA syndrome: management perspective with laparoscopic duodenojejunostomy and long-term results.

BACKGROUND: Superior mesentery artery syndrome (SMAS) is a rare vasculo-anatomic occlusive pathologic entity for which a period of conservative medical management is advocated with surgery reserved for nonresponsive cases. We present our management plan that entails a single admission approach and complete rendering of medical and surgical treatment to the patient on a background of the socioeconomic and cultural trends prevalent in this geographic region. METHODS: A retrospective analysis of 22 cases of SMAS admitted in our health care system who underwent a period of preoperative conditioning followed by laparoscopic duodenojejunostomy from September 2009 to June 2019 was performed. Patients were followed up at regular intervals. RESULTS: The mean follow-up of the cohort was 41.2 months (2-108 months). The median length of stay was 6 days. The mean postoperative stay was 4.13 days. A subgroup of six patients who had severe physiological depletion required a period of preoperative optimisation. Five of the 22 (22.7%) patients suffered from postoperative complications in the form of delayed return of bowel functions. None of the patients had complications more than Clavien-Dindo grade 2 with no mortality. Long-term data are available for 19 patients (86.3%) which showed no symptom recurrence. CONCLUSION: Management of SMAS that entails an antecedent medical therapy followed by surgery can be accomplished in a single admission with good to excellent results in the intermediate and long-term follow-up. Physiologically depleted patients do require a period of intensive preconditioning but on long-term follow-up, they have excellent results.

Transition metal chemistry of heavier group 14 congener triple-bonded complexes: syntheses and reactivity.

The diversification and synthetic utility of carbyne complexes in organometallic chemistry and catalysis are well recognized, but the syntheses of related heavier group 14 alkylidyne complexes are a recent advancement. A wide range of metal-ylidyne M[triple bond, length as m-dash]E (E = Si-Pb) complexes were synthesized and characterized spectroscopically. The synthetic methodology generally involves elimination or substitution chemistry between metallates and suitable group 14 precursors. The reluctance in forming triple bonded complexes makes this field quite fascinating and challenging. This article gives a brief overview of the pioneering reports followed by detailed information on the latest developments of complexes having a triple bond between a metal and heavier group 14 elements (Si, Ge, Sn, and Pb). Their synthesis and chemistry of the earlier reports followed by recent progress in this field will be discussed. Furthermore, their unique structures and bonding properties will be described based on spectroscopic and theoretical studies.

Dipropargyl substituted diphenylpyrimidines as dual inhibitors of monoamine oxidase and acetylcholinesterase.

Alzheimer's disease (AD) is a multifactorial neurological disorder involving complex pathogenesis. Single target directed drugs proved ineffective and since last few years' different pharmacological strategies including multi-targeting agents are being explored for the effective drug development for AD. A total of 19 dipropargyl substituted diphenylpyrimidines have been synthesized and evaluated for the monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibition potential. All the compounds were found to be selective and reversible inhibitors of MAO-B isoform. These compounds also displayed good AChE inhibition potential with IC50 values in low micromolar range. AVB4 was found to be the most potent MAO-B inhibitor with IC50 value of 1.49 ±â€¯0.09 µM and AVB1 was found to be the most potent AChE inhibitor with IC50 value of 1.35 ±â€¯0.03 µM. In the ROS protection inhibition studies, AVB1 and AVB4 displayed weak but interesting activity in SH-SY5Y cells. In the cytotoxicity studies involving SH-SY5Y cells, both AVB1 and AVB4 were found to be non-toxic to the tissue cells. In the molecular dynamic simulation studies of 30 ns, the potent compounds were found to be quite stable in the active site of MAO-B and AChE. The results suggested that AVB1 and AVB4 are promising dual inhibitors and have the potential to be developed as anti-Alzheimer's drug.

Healing of a large periapical lesion using triple antibiotic paste and intracanal aspiration in nonsurgical endodontic retreatment.

A patient with a large periapical lesion in relation to the maxillary right central and lateral incisors is presented here. During the conservative root canal treatment, aspiration of the fluid was done through the root canal, followed by placement of triple antibiotic paste for two weeks. Complete periapical healing was observed at the 24-month recall. This report confirms that for treatment of a large periapical lesion it is not always necessary to do surgical treatment and even cyst-like periapical lesions heal following conservative endodontic therapy.