SYNTHESIS OF FLAVONES FROM 2-HYDROXY ACETOPHENONE AND AROMATIC ALDEHYDE DERIVATIVES BY CONVENTIONAL METHODS AND GREEN CHEMISTRY APPROACH

Objective: Flavones occupy a special place in the realm of natural and synthetic organic chemistry owing to their diversified biological activities. In this study, a series of chalcone derivatives were synthesized and after cyclization of chalcone to synthesized various substituted flavone derivatives (2A-2L). 2 Methods: The reaction of 2-hydroxy acetophenone with substituted aromatic aldehydes produced chalcone by trituration (NaOH) and conventional methods (KOH/EtOH), which upon further cyclization with dimethyl sulfoxide/I  resulted to form flavone derivatives.Results: The purity of compounds was ascertained by melting point and thin-layer chromatography. The synthesized compounds have been characterized by mass, infrared, and1H nuclear magnetic resonance spectral analysis.Conclusion: Based on spectral data, it was proved that all synthesized chalcones and flavones derivatives meet the standard values of various spectral techniques and further it will be evaluated for pharmacological activities.Keywords: Chalcone, Flavone, Trituration, Conventional, Claisen-Schmidt condensation

3D Nanotemplates for Protein Crystallisation

This thesis presents the first experimental investigations into the combined effect of nanoscale surface porosity, narrow pore size distribution and surface chemistry, on nucleation and crystallisation of proteins. Co-operative self assembly of surfactants and silica was applied to prepare 3D nanotemplates with pore diameter 3.5±1.0nm, 5.5±1.5nm, 11.0±3.0nm, 16.0±3.0nm and 22.0±5.0nm. Post synthesis functionalisation was used to graft surface with -OH, -NH2, -CF3, -C6H5, - Cl and -CH3 functional groups. The relationship between 3D nanotemplate, N2 sorption and TEM pore diameter, XPS surface composition, wettability, surface charge and protein physicochemical properties was investigated, resulting in a coherent understanding of the combined effect of nucleant surface porosity and surface chemistry on protein crystallisation. The protein systems investigated for crystallisation include lysozyme, thaumatin, trypsin, albumin, concanavalin A, catalase and ferritin; varying in molecular weight from 14kDa – 450kDa and hydrodynamic diameter ~3-20nm. Crystallisation of proteins was found to be strongly dependent on 3D nanotemplate pore size. The 3D nanotemplate with a pore diameter similar to the protein’s hydrodynamic diameter (Dh) was found to be successful in preferential crystallisation, e.g. albumin (Dh=~5nm) and catalase (Dh=~10nm) was crystallised only on 5.5±1.5nm and 11.0±3.0nm 3D nanotemplates respectively. Here, we report a direct correlation between protein hydrodynamic diameter and 3D nanotemplate pore diameter, key for controlling protein nucleation. The correlation has been experimentally validated for all protein systems investigated. The concept of preferential crystallisation was further developed to investigate the applicability of this methodology for the separation of a target protein from a protein mixture. A solution of two proteins; porcine pancreatic lipase and RNAse was selected for this separation by crystallisation. Lipase (Dh=~4.5nm) and RNAse (Dh=~1.5nm) crystals were preferentially obtained with 5.5±1.5nm and 3.5±1.0nm 3D nanotemplates respectively. Furthermore, crystallisation of lipase from a commercially available crude source, (purity ~20%) containing a mixture of lipase, amylase and protease, was also achieved on the surface of the 5.5±1.5nm 3D nanotemplate. The significance of the work here is the demonstration that only specific nucleant surfaces with narrow pore size distribution can preferentially crystallise a target protein from a protein mixture, which is not possible with nucleants of broad pore size distribution, reported to be most suitable candidate for “universal nucleant”. Crystals of four out of the seven well studied proteins (lysozyme, albumin, concanavalin A and catalase) were obtained at lower protein concentration, whilst thaumatin was crystallised at par protein concentration but 3× lower precipitant concentration, on the surface of 3D nanotemplates functionalised with -OH, -CH3 and -NH2 functional groups. Here, we report that a reduction of 50- 92% protein concentration compared to the lowest reported literature values was achieved with the use of the 3D nanotemplates. As crystallisation was achieved for all seven protein systems at protein concentrations in the range of 2-20mg/mL, this approach can be used to engineer surfaces for preferential crystallisation of a target protein directly from industrial bioreactor broths. In summary, the findings of this thesis offer a first systematic approach for controlling the nucleation and crystallisation of biological macromolecules. The use of 3D nanotemplates offers the possibility of crystallising complex proteins (e.g. enzymes, antibodies, protein complexes, DAbs, MAbs) for structural determination and also novel crystallisation routes for downstream bioseparations

Identification of chalcone derivatives as putative non-steroidal aromatase inhibitors potentially useful against breast cancer by molecular docking and ADME prediction

Aromatase is an influential target to overcome estrogen receptor positive breast cancer, as the enzyme is responsible for conversion of androstenedione to estrone, a promising drug target for therapeutic management of breast cancer. Chalcones are prominent biosynthetic compounds and parent candidate for the synthesis of heterocycles with diversified biological activities. The prime objective of the present study is to evaluate the binding interaction of 2-hydroxyphenyl- prop-2-en-1-one (1A-1X), 2-hydroxy-4-methoxyphenyl- prop-2-en-1-one (3A-3X), 2,4-dihydroxyphenyl- prop-2-en-1-one (9A-9X) and 1-hydroxynaphthalen-2-yl-prop-2-en-1-one (5A-5X) derivatives with aromatase enzyme by molecular docking study and also check their ADME properties by maestro suit. The designed chalcones derivatives have been docked against our target protein with PDB id 3S7S retrieved from the protein data bank, whereas exemestane has been taken as the positive control. As docking data revealed that docking score of 1K, 1U, 1B 3K 3N, 5K, 5U, 9S, 9K, 9N and 9F compounds found less than exemestane and all of these compounds with appropriate ADME properties have proven their excellent absorption as well as solubility characteristics. The present findings provided valuable information about binding interactions of chalcones derivatives to the active site of aromatase. These compounds may serve as potential lead compound for developing new aromatase inhibitors in breast cancer treatment

Identification of chalcone derivatives as putative non-steroidal aromatase inhibitors potentially useful against breast cancer by molecular docking and ADME prediction

283-293Aromatase is an influential target to overcome estrogen receptor positive breast cancer, as the enzyme is responsible for conversion of androstenedione to estrone, a promising drug target for therapeutic management of breast cancer. Chalcones are prominent biosynthetic compounds and parent candidate for the synthesis of heterocycles with diversified biological activities. The prime objective of the present study is to evaluate the binding interaction of 2-hydroxyphenyl- prop-2-en-1-one (1A-1X), 2-hydroxy-4-methoxyphenyl- prop-2-en-1-one (3A-3X), 2,4-dihydroxyphenyl- prop-2-en-1-one (9A-9X) and 1-hydroxynaphthalen-2-yl-prop-2-en-1-one (5A-5X) derivatives with aromatase enzyme by molecular docking study and also check their ADME properties by maestro suit. The designed chalcones derivatives have been docked against our target protein with PDB id 3S7S retrieved from the protein data bank, whereas exemestane has been taken as the positive control. As docking data revealed that docking score of 1K, 1U, 1B 3K 3N, 5K, 5U, 9S, 9K, 9N and 9F compounds found less than exemestane and all of these compounds with appropriate ADME properties have proven their excellent absorption as well as solubility characteristics. The present findings provided valuable information about binding interactions of chalcones derivatives to the active site of aromatase. These compounds may serve as potential lead compound for developing new aromatase inhibitors in breast cancer treatment

A case series of percutaneous tension band wiring technique for fixation of fractures of olecranon and patella

There are several advantages in the treatment of fractures by means of closed reduction. Percutaneous fixation is a type of biological fixation. The aim and objectives of this study are to demonstrate the technique of percutaneous tension band wiring in cases of transverse, non- comminuted olecranon and patella fractures and to decrease the soft tissue dissection, blood loss, chances of infection and to ensure speedy mobilization using the innovative percutaneous fixation technique. This retrospective study includes ten patients of olecranon and ten patients of patella operated by the same surgeon. All patients were operated with percutaneous tension band wiring for olecranon and patella. There were six males and four females with olecranon fractures. There were seven males and three females who suffered patella fractures. The average duration of surgery was 55 minutes and average follow up was 24±6 weeks. The suture removal was done at 2 weeks. All patients had full range of movements at six weeks with significantly improved DASH score and Oxford knee score. None of the patients had any complications. Percutaneous fixation decreases the chances of bleeding secondary to unnecessary soft tissue dissection, thereby decreasing the post-operative morbidity. It also, convincingly, decreases the chances of post-operative infection and promotes early mobilization. Closed reduction with percutaneous fixation is believed to be an innovative, safe, reliable and efficient method of managing these difficult fractures

AN EXPOSITION OF MODERN INFORMATION SYSTEM AUDITS

ABSTRACT There is an ever increasing need for a systemized IT Architecture, in all the business developments in the current hour. The dependency on such architecture is inevitable, as every organization needs safe and secure transaction of data and information. IS Audit here, plays a major role, and it is one of the most prominent methods to maintain the integrity and authenticity of the information databases and transactions. This paper aims to provide an elucidation on the various processes, stages and types of IS audit

Analysis and Simulations of Abnormalities for Induction Motor Using PSCAD

Induction motors are most important part of any network or industry because most of the industries rely on this to drive their equipment. Due to various faults that take place in the motor it interrupts the normal functioning of the motor and leads to system failure or loss. So, it is necessary to reduce this stress factors to a safer level for normal functioning of the motor and this can be done by using various types of protective devices. In this paper we have mentioned different types of abnormalities and how to analyse these abnormalities using PSCAD. By simulating we can know proper working of any system and how that system would behave if same configuration existing at that time during fault. DOI: 10.17762/ijritcc2321-8169.150513

Molecular modeling and ADMET predictions of flavonoids as prospective aromatase inhibitors

192-200With the advent of a myriad of treatment possibilities for breast cancer, enzyme inhibition turns out to be the prevailing strategy for inhibiting estrogen biosynthesis. Aromatization of ring A of androstenedione, testosterone and 16-hydroxytestosterone results in increased estrogen level, which embraces the risk for breast cancer. In this present research, we have targeted human placental aromatase complexed with HDDG046 (PDB ID: 4GL7) for its inhibition by several inhibitors of flavonoid derivatives and further screening those molecules for ADMET properties for assessing its credibility for acceptance in successive steps of drug discovery. Novel flavonoid derivative molecules have been designed using Maestro 10.4, based on the literature review. Further, their molecular modeling studies have been performed against the imported target PDB ID: 4GL7 using the GLIDE platform and have been subjected to ADMET assessment using the QikProp and pkCSM program. From all the series exposed to molecular modeling; 2K, 4K, 6K, 8W and 10K molecules have been subjected to ADMET study based on their interaction profile. Successively screening of these molecules led to selection of 8W molecule for further validation by pkCSM. The results obtained have been compared with the reported molecule HDDG046 which presents substantially positive outcomes for 8W in terms of CaCo2 permeability, water solubility, P- glycoprotein; hERG I, II and CYP interactions, hepatotoxicity, LD50 value and so forth. Juxtaposing the results of all the designed molecules under study, we have established that these prospective molecules especially 8W of flavonoid derivatives have the potency to inhibit the target under study, which can be useful in the treatment of breast cancer. This has been estimated based on the in silico approaches performed using Molecular Modeling which utilizes the integral function of Molecular Mechanics and Quantum Mechanics. In addition, the ADMET predictions validate their integrity for being the lead molecules in drug discovery stages in the near future

Author Correction: Federated learning enables big data for rare cancer boundary detection.

10.1038/s41467-023-36188-7NATURE COMMUNICATIONS14