Hemisection- A Window Of Hope For A Perishing Tooth

Mandibular first molars are the most commonly extracted teeth due to dental caries and periodontal disease. These teeth are the major standpoint for occlusion, and also have a wide peri-cemental area. Hence, any defect in the root either mesial or distal, extraction is the most common treatment planned. Under specific conditions, only the diseased part of the tooth can be extracted after an endodontic treatment. A modified fixed partial denture design is fabricated to splint the remaining portion of the tooth to adjacent teeth. This procedure though donting can be easily achieved and maintained successfully

Squash cytology in neurosurgical practice: a useful method in resource-limited setting with lack of frozen section facility

BACKGROUND: Intra-operative cytology is an important diagnostic tool. It has shown to play an important role especially in the diagnosis of central nervous system tumours. The study was done to assess the feasibility of squash cytology as standalone diagnostic test in setting where frozen section facility is not available. MATERIALS AND METHODS: Total 48 patients with various intracranial lesions were initially enrolled in the study. Patients were investigated by various radio-imaging techniques and routine blood investigations. Forty-one patients were operated at Netaji Subhash Chandra Bose medical college, Jabalpur. Intra-operative squash cytology diagnosis was performed and was correlated with histology diagnosis as gold standard. RESULTS: Out of 41 patients, inflammatory lesions were diagnosed in nine patients while benign lesions [most common neurilemmoma and meningioma] were observed in 21 and malignant lesions [astrocytoma was most common] were diagnosed in 11 patients. Diagnostic accuracy of intra-operative squash cytology irrespective of lesion & site was 95%. We were able to inform about the diagnosis to neurosurgeon in 15 minutes in all cases and within 12 minutes in >85% cases CONCLUSION: Squash smear cytology is reliable and rapid standalone diagnostic method and it can assist for intra-operative decision-making diagnosis of intracranial lesions in resource-limited settings where frozen section facility is not available

Quinazolin-4-one derivatives lacking toxicity-producing attributes as glucokinase activators: design, synthesis, molecular docking, and in-silico ADMET prediction

Abstract Background A small library of quinazolin-4-one clubbed thiazole acetates/acetamides lacking toxicity-producing functionalities was designed, synthesized, and evaluated for antidiabetic potential as glucokinase activators (GKA). Molecular docking studies were done in the allosteric site of the human glucokinase (PDB ID: 1V4S) enzyme to assess the binding mode and interactions of synthesized hits for best-fit conformations. All the compounds were evaluated by in vitro enzymatic assay for GK activation. Results Data showed that compounds 3 (EC50 = 632 nM) and 4 (EC50 = 516 nM) showed maximum GK activation compared to the standards RO-281675 and piragliatin. Based on the results of the in vitro enzyme assay, docking studies, and substitution pattern, selected compounds were tested for their glucose-lowering effect in vivo by oral glucose tolerance test (OGTT) in normal rats. Compounds 3 (133 mg/dL) and 4 (135 mg/dL) exhibited prominent activity by lowering the glucose level to almost normal, eliciting the results in parallel to enzyme assay and docking studies. Binding free energy, hydrogen bonding, and π–π interactions of most active quinazolin-4-one derivatives 3 and 4 with key amino acid residues of the 1V4S enzyme were studied precisely. Preliminary in-silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction was carried out using SwissADME and PreADMET online software which revealed that all the compounds have the potential to become orally active antidiabetic agents as they obeyed Lipinski's rule of five. Conclusion The results revealed that the designed lead could be significant for the strategic design of safe, effective, and orally bioavailable quinazolinone derivatives as glucokinase activators. </jats:sec

Quinazolin-4-one derivatives lacking toxicity-producing attributes as glucokinase activators: design, synthesis, molecular docking, and <i>in-silico</i> ADMET prediction

Background A small library of quinazolin-4-one clubbed thiazole acetates/acetamides lacking toxicity-producing functionalities was designed, synthesized, and evaluated for antidiabetic potential as glucokinase activators (GKA). Molecular docking studies were done in the allosteric site of the human glucokinase (PDB ID: 1V4S) enzyme to assess the binding mode and interactions of synthesized hits for best-fit conformations. All the compounds were evaluated by in vitro enzymatic assay for GK activation. Results Data showed that compounds 3 (EC50 = 632 nM) and 4 (EC50 = 516 nM) showed maximum GK activation compared to the standards RO-281675 and piragliatin. Based on the results of the in vitro enzyme assay, docking studies, and substitution pattern, selected compounds were tested for their glucose-lowering effect in vivo by oral glucose tolerance test (OGTT) in normal rats. Compounds 3 (133 mg/dL) and 4 (135 mg/dL) exhibited prominent activity by lowering the glucose level to almost normal, eliciting the results in parallel to enzyme assay and docking studies. Binding free energy, hydrogen bonding, and pi-pi interactions of most active quinazolin-4-one derivatives 3 and 4 with key amino acid residues of the 1V4S enzyme were studied precisely. Preliminary in-silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction was carried out using SwissADME and PreADMET online software which revealed that all the compounds have the potential to become orally active antidiabetic agents as they obeyed Lipinski's rule of five. Conclusion The results revealed that the designed lead could be significant for the strategic design of safe, effective, and orally bioavailable quinazolinone derivatives as glucokinase activators

Hetero-substituted sulfonamido-benzamide hybrids as glucokinase activators: Design, synthesis, molecular docking and <i>in</i>-<i>silico</i> ADME evaluation

A series of hetero-substituted sulphonamido-benzamide derivatives which can activate glucokinase (GK) were synthesized and screened in-vitro using Human GK activation assay and in-vivo following oral glucose tolerance test (OGIT) assays. All the molecules were docked into the active site of 1V4S receptor grid by XP docking method utilizing Schrodinger software to assess the binding interactions. Compounds 12 (EC50 = 495 nM) and 15 (EC50 = 522 nM), revealed maximum in-vitro GK activation. Selected compounds were subjected for in-vivo OGIT assay. The data revealed that same compounds 12 (135 mg/dL) showed maximum reduction in blood glucose level followed by compound 15 (142 mg/dL) at 120 min. The docking results as glide score, binding energy and interactions were reported and compounds with maximum pharmacological activity were studied precisely. In-silico ADME parameters, pharmacokinetic properties and toxicity studies were carried out and all compounds were found to have good bioavailability and nontoxic. Overall, the series of hetero-substituted sulphonamido-benzamide hybrids are safe and could be explored further for better therapeutic efficacy as GK activators. (C) 2020 Elsevier B.V. All rights reserved.University Grant Commission, Indi

Strategic analyses to identify key structural features of antiviral/antimalarial compounds for their binding interactions with 3CLpro, PLpro and RdRp of SARS-CoV-2: <i>in silico</i> molecular docking and dynamic simulation studies

Severe acute respiratory syndrome coronavirus (SARS-CoV-2), a novel member of the betacoronavirus family is a single-stranded RNA virus that has spread worldwide prompting the World Health Organization to declare a global pandemic. This creates an alarming situation and generates an urgent need to develop innovative therapeutic agents. In this context, an in silico molecular docking and molecular dynamics (MD) simulation study on the existing 58 antiviral and antimalarial compounds was performed on 3CLpro, PLpro and RdRp SARS-CoV-2 proteins. The antiviral compounds are best fitted in the binding pockets and interact more profoundly with the amino acid residues compared to antimalarial compounds. An HIV protease inhibitor, saquinavir showed a good dock score and binding free energy with varied binding interactions against 3CLpro and PLpro. While, adefovir, a nucleotide HBV DNA polymerase inhibitor exhibited good dock score and binding interactions against RdRp. Although, the antimalarial compounds showed relatively less dock score but were found to be crucial in displaying essential binding interactions with these proteins. The MD simulation runs for 100 ns on 3CLpro–saquinavir, PLpro–saquinavir and RdRp–adefovir complexes using Desmond revealed fairly stable nature of interactions. This study helped in understanding the key interactions of the vital functionalities that provide a concrete base to develop lead molecules effective against SARS-CoV-2. Communicated by Ramaswamy H. Sarma</p

In-silico studies of 2-aminothiazole derivatives as anticancer agents by QSAR, molecular docking, MD simulation and MM-GBSA approaches

Targeting Hec1/Nek2 is considered as crucial target for cancer treatment due to its significant role in cell proliferation. In pursuit of this, a series of twenty-five 2-aminothiazoles derivatives, along with their Hec1/Nek2 inhibitory activities were subjected to QSAR studies utilizing QSARINS software. The significant three descriptor QSAR model was generated, showing noteworthy statistical parameters: a correlation coefficient of cross validation leave one out (Q2LOO) = 0.7965, coefficient of determination (R2) = 0.8436, (R2ext) = 0.6308, cross validation leave many out (Q2LMO) = 0.7656, Concordance Correlation Coefficient (CCCCV = 0.8875), CCCtr = 0.9151, and CCCext = 0.0.7241. The descriptors integral to generated QSAR model include Moreau-Broto autocorrelation, which represents the spatial autocorrelation of a property along the molecular graph’s topological structure (ATSC1i), Moran autocorrelation at lag 8, which is weighted by charges (MATS8c) and RPSA representing the total molecular surface area. It was noted that these descriptors significantly influence Hec1/Nek2 inhibitory activity of 2-aminothiazoles derivatives. New lead molecules were designed and predicted for their Hec1/Nek2 inhibitory activity based on the developed three descriptor model. Further, the ADMET and Molecular docking studies were carried out for these designed molecules. The three molecules were selected based on their docking score and further subjected for MD simulation studies. Post-MD MM-GBSA analysis were also performed to predicted the free binding energies of molecules. The study helped us to understand the key interactions between 2-aminothiazoles derivatives and Hec1/Nek2 protein that may be necessary to develop new lead molecules against cancer. Communicated by Ramaswamy H. Sarma</p