Lung Cancer remains a significant health concern, necessitating the exploration of novel therapeutic avenues due to the limited efficacy and adverse effects of current treatments. In this study, we utilized a thorough in-silico and in-vitro methodology to develop prospective drugs for the treatment of lung cancer. The active components of Citrus latifolia were identified through the utilization of a variety of pharmacological instruments, such as Gene Ontology, GeneCards, DrugBank, the Chinese Traditional Drug Database, and GeneMANIA. Subsequent molecular docking studies using GOLD software revealed Hesperidin as the most promising candidate, exhibiting a remarkable binding affinity (GOLD score: 60.98 kcal/mol) towards the epidermal growth factor receptor (EGFR), a pivotal target in lung cancer therapy. Further validation through Schrodinger-Glide redocking reaffirmed the robust interaction between Hesperidin and EGFR. Pharmacokinetic profiling of top-scoring ligands indicated favorable drug-like properties, supporting their therapeutic potential. Molecular dynamics simulations employing Desmond software demonstrated the structural stability and persistence of the Hesperidin-EGFR complex over a 100-ns trajectory, corroborating its efficacy. Additionally, cytotoxicity analysis revealed a potent inhibitory effect of Hesperidin with an IC50 value of 34.25 µg/ml. Collectively, our findings underscore Hesperidin from Citrus latifolia as a promising candidate for lung cancer therapy, warranting further investigation through in-vivo studies for clinical translation.
Prostate cancer is the second most dangerous cancer type worldwide. While various treatment options are present i.e. agonists and antagonists, their utilization leads to adverse effects and due to this resistance developing, ultimately the outcome is remission. So, to overcome this issue, we have undertaken an in-silico investigation to identify promising and unique flavonoid candidates for combating prostate cancer. Using GOLD software, the study assessed the effectiveness of 560 natural secondary polyphenols against CDKN2. Protein Data Bank was used to retrieve the 3D crystal structure of CDKN2 (PDB Id: 4EK3) and we retrieved the structure of selected secondary polyphenols from the PubChem database. The compound Diosmetin shows the highest GOLD score with the selected Protein i.e. CDKN2 which is 58.72. To better understand the 2-dimensional and 3-dimensional interactions, the interacting amino acid residues were visualised using Discovery Studio 3.5 and Maestro 13.5. Using Schrodinger-Glide, the Diosmetin and CDKN2 were re-docked, and decoy ligands were docked to CDKN2, which was used to further ascertain the study. The ligands with the highest Gold score were forecasted for pharmacokinetics characteristics, and the results were tabulated and analysed. Utilising the Gromacs software and Desmond packages, 100 ns of Diosmetin molecular dynamics simulations were run to evaluate the structural persistence and variations of protein-ligand complexes. Additionally, our investigation revealed that Diosmetin had a better binding affinity with CDKN2 measuring 58.72, and it also showed remarkable stability across a 100-ns simulation. Thus, following in-vitro and in-vivo clinical studies, diosmetin might lead to the Prostate regimen.Communicated by Ramaswamy H. Sarma
Qatar is a country located on the east shores of the Arabian Peninsula. In the past three decades, Qatar has experienced significant changes in its educational and healthcare systems. At the time of writing this paper, there are two accredited Faculties of Medicine, which offer students from all over the world the possibility of becoming doctors. Residency Programs are taught in English and are accredited by Accreditation Council for Graduate Medical Education-International (ACGME-I). In this paper, we outline the organisation of Qatar medical education at undergraduate and postgraduate levels, with particular emphasis on the postgraduate anaesthesiology residency program. We outline the opportunities for curriculum development and its future challenges.
Pavements have mainly two types i.e. rigid pavement and flexible pavement. Flexible pavements constructed with bituminous as binder and aggregate materials. Bitumen is a viscous mixture of hydrocarbons obtained naturally or as a residue from petroleum distillation, used for road surfacing and roofing. Bitumen is non-hazardous under normal conditions but when heated it becomes toxic and has consequences of environmental degradation. Also being a non-renewable source of energy, will lead to depletion of petroleum reserves. It is a key challenge in highway industry to reduce the dependence on fossil fuels & to recycle the highway waste. The asphalt industry is a sector that has a sustainable environmental impact, one of the main components being binder, i.e. bitumen, which is produced from petroleum. Bitumen generation leads to enormous amounts of carbon dioxide emission which causes hazardous environmental impact. This research is about to reduce the load on environment by the use of waste material i.e. waste cooking oil and waste engine oil. This research will help to find out the optimum addition percentage of waste material to bituminous concrete mix. This research is a way towards sustainable environment.
Type 2 Diabetes mellitus (T2DM) is a globally leading metabolic problem with increased morbidity and mortality. Current medication therapies in the market to control diabetes are not sufficient and therefore, there is further need to develop more selective and effective treatment approaches. Inhibition of Dipeptidyl-peptidase-IV (DPP-IV) enzyme may serve as an interesting target for developing novel anti-diabetic drug candidate. In the present study, hierarchical virtual screening of drug like compounds was done followed by molecular dynamics simulation and knowledge-based structure-activity relation (SAR) study in order to retrieve hit compound as prospective inhibitors of DPP-IV enzyme. Important amino acid residues present in the active target site were acknowledged as vital and were also found to have similar interactions with the potential hits. Further, in silico technique was undertaken to identify ubiquitous promising hits against DPP-IV enzyme and this was followed by calculation of binding energy and absorption, distribution, metabolism, excretion (ADME) prediction that could possibly support their pharmacokinetic prospective. Furthermore, stability study using molecular dynamics simulation of protein complex was accomplished with the most capable targeted hit established in the present study. In the end, comparative analysis of 3-dimensional binding pose, orientation and planar structure of the potential retrieved hit was done with marketed drugs (alogliptin and sitagliptin) in order to develop knowledge-based structure-activity relationship, which proved the successful designing of DPP-IV enzyme inhibitors.
Aims: To compare the clinical and radiological outcome of extra-articular proximal tibial fractures treated with Intramedullary Nail And Minimally Invasive Percutaneous Plate Osteosynthesis with objectives -To assess the outcome in terms of fracture union by means of clinical and radiological features and outcome after surgical procedures, complications in these two methods of treatment Methods: Our study consists of 40 cases of extra-articular proximal tibia fractures. All cases aged were more then 18 were operated at Sanjay Gandhi Institute of trauma and orthopaedics from December 2017 to June 2019.Clinical outcome was assessed through knee society score. All the cases in the study were post-traumatic. Mean duration of follow up was 6 months. Results: Out of 40 patients, 36 were males and 4 were females. Average age of the patients was 38.40 years and 38.30 years in MIPPO group and IMN group respectively. 57.5% of the patients sustained a right sided fracture and 42.5% had left sided fracture. Mean knee society score of group 1 and group 2 at all visit of follow-up i.e 1 month, 2 month, 3 month, 6 month and 12 month were not significantly different from each other. Complication in both groups was also comparable. Conclusion: Extra- articular Proximal tibial fractures can be effectively treated by interlocking intra medullary nails with multi directional locking options as well as with MIPPO with excellent results, There is no significant difference between two mode of treatment as far as early post-operative mobilization, intra operative blood loss, Hospital stay, knee society score and complication. The operative technique was simple and short. No significant difference were there in complications encountered in our study. It can be concluded that both the technique were equally effective and choice of methods depends on the surgeon own experience, setup and patient choice.
Solar colletors of Flat Plate type is a thermal transfer device that absorbs solar radiation and converts it into heat, which is mainly used to increase the water temperature, heat and dryness, dryness of crops in the region, space heating and in industries where this hot fluid is required for many chemical reactions, and for applications requiring the temperature of the fluid to be less than 100°C. As non-renewable sources of energy are becoming depleted and will soon have the power crisis. So, referring to fatigue rates, we should use our entire renewable resources so that we can control the rate of decline. The main components of the flat plate air collector are, absorbing plate, top covering plate (glass cover), insulating material and channel pipes covered with insulating material. Absorber plates are covered with a high absorbent coating. The top cover should be made of a maximum transmittance. The effectiveness of the flat plate air collector is highly affected by the losses through the top covering material and also due to the low heat transfer coefficient between the absorber plate and the air flowing through it. Most of the experiments and studies have shown that efficiency can be increased by using different types of solar collector which include double pass, a single pass with fins etc. Based on the literature survey it has been found that most of the studies on the solar collector are done to increase its thermal efficiency by enhancing the rate heat transfer between air and the absorber plate by using rough surface on the absorber plate.
Background:The humans can be affected by more than 100 types of cancers in which about 22 % cancer death are caused by tobacco, 10% due to alcohol and obesity, 5-10 % by genetic defects and 20 % by infections. Rheumatoid arthritis, an autoimmune disorder, occurs mostly in middle age, affects 2.5 times more to females than males and till 2015, more than 24.5 Million people get affected from this disorder. The deaths due to rheumatoid arthritis were 28000 in 1990 and increased to 38000 in 2013. Parkinson’s disease, a neurodegenerative disorder of central nervous system affects about 6.2 million people in 2015 and responsible for approximately 117400 deaths worldwide. Parkinson’s disease occurs mainly over the age of 60 and males get more affected than females.Methods:Bibliographic database has created by mendeley desktop software for available literature in peer reviewed research articles especially by titles and disease names as keywords with AND Boolean operator (title AND year or author AND year). The intervention and findings of quality papers were extracted by detailed study and a conceptual framework has developed.Results:Total 121 research and review articles are cited in this review to produce high impact in literature for pathophysiology and receptors involved in all three diseases. Changes in enzyme action, prohibition of angiogenesis and inhibition of microtubule are the main areas where anticancer molecules may perform significant effect. The immune system is not a good target for rheumatic treatment due to many complications that occur in body but fibroblast, like synoviocytes, proteases which are responsible for cartilage destruction and osteoclast differentiation may be the beneficial targets for pharmacoactive molecules in the treatment of rheumatoid arthritis. In Parkinson’s disease, supply of dopamine to brain from outside results in brain dopamine synthesis decrement which increase drug dependency. The compounds which stimulate secretion, reuptake inhibitor and increment in dopaminergic neurons may be good targets.Conclusion:Alteration of signal transduction by a drug is the goal of chemogenomics, a new branch formed by combination of chemistry and genomics. The proliferation, angiogenesis and apoptosis of cancer cells are regulated by cellular signaling of transcription factors, protein kinases, transmembrane receptors, extracellular ligands and some external factors like oncogenic mutations, ubiquitin-proteasome pathway with epigenetic changes. Traditional anticancer drugs either alter DNA synthesis or control cell division while new drugs retard tumor growth or induce apoptosis. The deterioration of dopaminergic neurons in substantia nigra results in Parkinson’s disease with mental confusion, cognitive dysfunction and sleep disorder. Rheumatoid arthritis is characterized by inflammation, autoimmunity, joint destruction, deformity and premature mortality and treated mainly by anti-inflammatory and antirheumatic drugs. This review provides a comprehensive summary of objects which may act as potential targets for many health disorders.
Secondary benzylic alcohols represent a challenging class of substrates for N-alkylation of amines. Herein, we describe an iron(II)-catalyzed eco-friendly protocol for N-alkylation of secondary arylamines with secondary benzyl alcohols through a carbocationic pathway instead of the known borrowing hydrogen transfer (BHT) approach. Transiently generated carbocations, produced from alcohols via self-condensation, were coupled with arylamines to provide highly functionalized amine products. The scope of this methodology involves N-alkylation of primary, secondary and heterocyclic amines with primary/secondary benzylic, allylic and heterocyclic alcohols, which are common key structures in numerous pharmaceuticals drugs. The method can also be easily adopted for the amination of various natural products.
A novel, green and transition metal-free reduction of nitroarenes has been explored. 2-Aminoquinazolin-4(3H)-one and its derivatives have been first time investigated as hydrogen bonding organocatalysts for the activation of hydrazine hydrate to reduce nitroarenes.
The potential of 2-aminoquinazolin-4(3H)-one as an organocatalyst for the activation of aldehydes via noncovalent interaction for the synthesis of tertiary amines using formic acid as a reducing agent is reported for the first time. The developed protocol demonstrated a dilated substrate scope for aromatic and aliphatic amines with aromatic and aliphatic aldehydes. Furthermore, the current method was also fruitful for the derivatization of ciprofloxacin and its derivative in good to excellent yields.
2-Aminoquinazolin-4-one based efficient organocatalytic eco-friendly reductive amination approach was developed for the mono N-alkylation of anilines using hydrosilane as a reducing agent. This practically easy and sustainable approach works under neat reaction conditions and utilizes non-toxic environmentally benign acetic acid as a dehydrating agent. The developed protocol have several advantages, such as broad substrate scope, wide functional group tolerance, short reaction time, and absence of metal catalyst in the reaction.
120Microalgae are also known for third generation biofuel as well as alternative feedstock because some species contain high percentage of lipid content, which could be extracted from their cells, processed and esterified into transportation fuels by using currently developed technology; they have high biomass, permit the use of nonarable land and unpotable water, use far less water and do not displace food crop cultures; the production of this organism is not depending on the season and it can be easily harvested. Bioprospecting of microalgal strains encompasses searching, collection and preservation of unique strains from different aquatic environments for exploiting the potential applications of nutraceuticals, value-added products such as polyunsaturated fatty acids (PUFA). High lipid contents were extracted from the biomass through different solvent extraction methods and the composition of individual fatty acids had been found out through gas chromatography–mass spectrometry (GC-MS) analysis based on their retention time and molecular weight. These results make a better understanding of rapid metabolic responses in the percentage of saturated fatty acids (SFA), PUFA and mono unsaturated fatty acids (MUFA).
Background: Clobazam (CLB) has been used as an anxiolytic, anticonvulsant and antiepileptic drug under the trade names, Frisium, Urbanol, Onfi and Tapclob. Impurity profiling in the pharmaceutical industries is a central task in the manufacturing of drug product. The quantification of impurities in active pharmaceutical ingredients (APIs) is also receiving considerable importance from the regulatory authorities in the point of stringent quality requirement. Thus, the provision of substantial quantity of impurities as standards, which are accomplished either by isolation from crude reaction mass or the synthesis of material with proposed structure using new synthetic route, to analytical method development and validation is a good demand. Therefore, easily accessible synthetic routes to the preparation of impurities with the lowest cost are sought after. To date, no synthetic specifics were found on the synthesis and characterization of CLB Imp-B, -C, -D and -F, and the synthesis of CLB Imp-E. Therefore, the comprehensive study was undertaken on the synthesis and characterization of CLB related impurities and this study might be useful to prepare CLB impurities in the required quantity with purity to use as a reference standard of analytical method development in pharmaceutical industry. Methods: The synthetic routes were developed for the synthesis of CLB impurities such CLB Imp-B to Imp-F and isolated them using purification techniques with purity in the required quantity. The commercially available key starting materials, reagents and solvents were used in the course of synthesis of impurities. The analytical techniques such as NMR, IR and mass were used to characterize the structure of synthesized CLB related impurities. Results: The easy accessible synthetic methods were developed for the synthesis of clobazam related impurities, CLB Imp-B to F in good to excellent yields with purity as well as described the cause to formation of these impurities. The KSM related impurity, 2-chloro-1-nitrobenzene and the active methylene hydrogens in clobazam are caused to the formation of CLB Imp-B and CLB Imp-C&-D, respectively. CLB Imp-E and -F are formed due to the degradation of drug molecule, CLB in the presence of base (NaOH). CLB Imp-B was prepared from 2-chloro-1-nitrobenzene by following similar process of CLB reported in the synthetic specific. CLB Imp-F was prepared from 5-chloro-N'-phenylbenzene-1,2-diamine by coupling with mono-methyl malonate followed by N-methylation using dimethyl sulfate. The rest of all impurities were planned to prepare by taking CLB as starting material. CLB Imp-C and -D were synthesized by treating CLB with methyl iodide in the presence of inorganic base. The mixture of aqueous NaOH and CLB was agitated vigorously at 75-80 degrees C to obtain CLB Imp-E. All the synthesized compounds were purified using purification techniques such as crystallization and column chromatography, and well characterized by IR, ESI-mass, H-1 NMR, C-13 NMR and DEPT analyses. Conclusion: The immaculate discussion about synthetic approaches and structural elucidation using analytical applications such as IR, NMR (H-1, C-13 and DEPT) of CLB Imp-B to F, which are listed in the European pharmacopoeia monograph of clobazam, has been described. All the impurities were obtained with stringent purity (>98%) in the described synthetic routes and the same impurities have been used in analytical method development in our pharmaceutical industry. Also, the plausible mechanistic path ways to the formation of impurities, keeping in view the regulatory importance of clobazam, were discussed in detail.
The present study is related to a commercially practicable new synthetic process for production of teneligliptin hydrobromide hydrate (1), a dipeptidyl peptidase-4 (DPP-4) inhibitor. Key strategies in the new process include preparation and isolation of new intermediates such as a better reactive nosyl derivative (3c) of l-proline methyl ester (2), its stereoselective substituted intermediate (5) with 1-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazine (4) through SN2-type nucleophilic substitution, and isolation of carboxylic acid derivative 6 by deesterification of intermediate 5. The reaction conditions for preparation of new intermediates, and the additionally used coupling reaction for amidation and deprotection of N-Boc were optimized with control of impurities to improve the quality of drug molecule 1 with good yield. The developed synthetic strategy offers significant advantages over existing synthetic approaches, avoiding use of expensive reagents, long time consumption, and laborious procedures involving isolation of intermediates. The developed process for drug molecule 1, achieving overall yield of 37–39% over six sequential chemical transformations, enables rapid delivery of multi-kilogram quantities of the desired active pharmaceutical ingredient (API), meeting stringent purity requirements.
Chilaiditi sign and syndrome are uncommon conditions and often misdiagnosed. They are clinically significant, however, because they can result in a range of complications, including bowel volvulus, perforation and obstruction. When patients are symptomatic, treatment is usually conservative and surgery is rarely indicated unless there is a suspicion of ischaemia, or if conservative management does not resolve other signs and symptoms. This article describes Chilaiditi sign and syndrome, and presents four case studies to illustrate the relevant signs and symptoms.
Spirulina/Arthrospira is a species of cyanobacteria used in health foods, animal feed, food additives and fine chemicals. The present study conducted a comparison of the 16S rRNA and cpcBA-intergenic spacer (cpcBA-IGS) gene sequences in Spirulina/Arthrospira strains from culture collection of CCUBGA, IARI, New Delhi. All the strains of Spirulina used in this study had shown nearly 99% similarity amongst them. About fifty sequences (cpcBA-IGS) of Spirulina strains taken from NCBI with ten from the present strains of Spirulina, a neighbour-joing (NJ) tree was constructed with the help of MEGA5.0. The tree showed 99% similarity. All the sequences were put to Multiple Sequence Alignment with the help of T-Coffee (version 7.38) and BioEdit (version 7.38) software. Similarity studies undertaken based upon 16S rRNA and cpcBA-IGS genes sequence analysis indicated similarity coefficient of 0.84. S. platensis and Arthrospira sp. showed 100 percent similarity. Therefore, the current study supports some previous conclusions based on 16S rRNA gene and cpcBA-IGS sequences, which found that Arthrospira taxa are monophyletic. However, compared to 16S rRNA sequences, cpcBA-IGS sequences might be better suited to resolve close relationships and interspecies variability.