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BACKGROUND: Inhibiting receptor-tyrosine-kinase (RTK) signalling pathways has emerged as a key focus of novel cancer therapy development. Vascular endothelial growth factor receptor (VEGFR) is a member of the RTK family and is required for vasculogenesis and angiogenesis. Because VEGFR 2 is the subtype responsible for cellular angiogenesis and vasculogenesis, blocking it will impair tumour cell blood supply, reducing their development, proliferation, and metastasis. AIM & OBJECTIVE: The aim of this study is to obtain an optimised pharmacophore as a VEGFR2 inhibitor using QSAR investigations. This aids in determining the link between structure and activity in new chemical entities (NCEs). MATERIALS AND METHODS: The multi-linear regression approach (MLR) method was utilised to generate the QSAR Model using the programme QSARINS v.2.2.4. RESULTS AND DISCUSSION: For 2D QSAR, the best models produced has correlation coefficients of R2= 0.9396. The 3D-QSAR model obtained with R2= 0.9121 and Q2 = 0.8377. Taking docking observations, pharmacological behaviour, and toxicity analyses into account, most of the derivatives demonstrated VEGFR2 inhibitory competence. CONCLUSION: According to QSAR studies, more electron-donating groups on the benzene ring linked to the isoxazole were shown to be necessary for activity. In molecular docking studies, most compounds have shown stronger affinity for the crucial amino acids Cys:919, Asp:1046, and Glu:885, which are found in typical drugs. All NCEs passed the Lipinski screening.

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BACKGROUND: Every year Invasive Fungal Infections (IFI) are globally affecting millions of people. Candida albicans and Aspergillus niger have been reported as the most infectious and mortality-inducing fungal strains among all pathogenic fungi. AIMS & OBJECTIVES: To tackle this problem in the current study Pyranopyrazoles and Pyrazolopyrano- pyrimidine derivatives were developed using molecular hybridization, green chemistry and one-pot multicomponent reaction. MATERIALS AND METHODS: In the present work, New Chemical entities (NCE's) were developed on the basis of Structure activity relationship. All designed NCE's were screened for ADMET studies using the QikProp module of Schrodinger software. NCE's with zero violations were further docked on the crystal structure of 14α demethylase, cytochrome P450 and thymidine synthase (PDB ID: 5V5Z, 7SHI, 1BID). Selected molecules were synthesized using green chemistry techniques and evaluated for in vitro antifungal activity against Candida albicans and Aspergillus niger. RESULTS AND DISCUSSION: Designed NCE's (B1-12 and C1-11) showed favorable results in ADMET studies. In the docking study six compounds from series-B and five molecules from series- C showed good dock score and binding interaction when compared with the standard drugs. Compounds B-3 and C-4 showed the highest zone of inhibition activity against Candida albicans, where as B-1 and C-3 had shown highest zone of inhibition activity against Aspergillus niger. CONCLUSION: Bicyclic ring (series B) showed better activity as compare to fused tricyclic ring (series C).

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BACKGROUND: Cancer is a devastating disease. Many studies have shown that the primary causes of the aggressive and resistant types of cancer are the overexpression of receptors and growth factors, activation of oncogenes, and the inactivation of tumour suppressor genes. One such receptor is the epidermal growth factor receptor (EGFR), which is used as a drug target for the treatment of cancer. OBJECTIVE: This study aimed to develop the new chemical entities of amide derivatives of chalcone as EGFR inhibitors using structure-activity relationship (SAR) studies, molecular docking, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) studies. METHOD: New chemical entities (NCE) were designed based on literature findings. The Schrodinger 13.4 software was used for the molecular docking study. While Quickprop and Pro Tox-II online tools were used for ADME and toxicity prediction, respectively. RESULT: In this work, all compounds were subjected to an in-silico ADMET analysis. After pharmacokinetic and toxicity profile predictions, the molecules were further analysed by molecular docking. As a result of molecular docking, molecules AC9 and AC19 showed comparable docking scores compared to standard Afatinib. CONCLUSION: Molecules AC9 and AC19 showed good docking scores and a promising ADMET profile. In the future, these derivatives can be further evaluated for wet lab studies and determination of their biological activity.

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BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the joints, leading to pain, swelling, and joint deformity. Effective management of RA involves the use of disease-modifying drugs that can slow down disease progression and alleviate symptoms. Among the potential targets for RA treatment is Bruton's tyrosine kinase (BTK), which plays a crucial role in B-cell signalling and contributes to the pathogenesis of RA. AIMS: QSARINS (QSAR-INSUBRIA) is software used for the development and validation of Quantitative Structure-Activity Relationship (QSAR) analysis. In the present work, this software was explored for pharmacophore optimization of the pyrrolo-pyrimidine nucleus for anti-rheumatoid activity. METHODS: A series of pyrrolo-pyrimidine derivatives were used to build the QSAR models. These models were generated to identify structural features that correlate significantly with the activity. We followed the assessment of statistical parameters to ensure thorough validation of all the QSAR models. The QSAR models demonstrating better statistical performance were selected, and descriptors of these models were analysed. RESULTS: The results showed that the QSAR models were highly statistically robust and exhibited a strong external predictive ability. Their structural features were also deduced. CONCLUSION: This QSAR study provided crucial information about the specific molecular features that can be used for the optimization of the pharmacophores. This research provides valuable insights into the structural features essential for BTK inhibition and paves the way for the design and development of novel anti-rheumatic agents targeting BTK in RA.

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INTRODUCTION: Curcumin, an anticancer natural compound with multiple pharmacological activities, has a weak pharmacokinetic and instability due to diketone moiety. Curcumin's stability challenges can be overcome by removing the diketone moiety and shortening the 7-carbon chain, resulting in mono-carbonyl analogs. Cancer proliferation is caused by the activation of Epidermal Growth Factor (EGFR) pathways. Current available EGFR inhibitors have an issue of resistance. AIM: Thus, we aimed to design new mono-carbonyl curcumin derivatives and analyse their drug likeness properties. Further, to investigate them on three distinct crystal structures, namely two wild-type and L858R/T790M/C797S mutant generations for EGFR inhibitory activity. METHOD: Ten New Molecular Entities (NME's) were designed using literature survey. These molecules were subjected to comparative molecular docking, on the EGFR crystal structures viz. wild-type (PDB: 1M17 and 4I23) and L858R/T790M/C797S mutant (PDB: 6LUD) using Schrodinger software. The molecules were also tested for Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties. The docked complex of the hit molecule was studied for molecular simulation. RESULT AND DISCUSSION: In molecular docking studies, NMEs 1, 2, and 3 were found to have good binding affinity with 1st , 2nd , and 3rd generation EGFR crystal structures and a greater dock score than standard curcumin. All molecules have shown a good ADMET profile. Since L858R/T790M/C797S is currently being explored more, we decided to take the best molecule, NME 3, for molecular dynamics with 6LUD, and the results were compared with those of the co-crystallized ligand S4 (Osimertinib). It was found that the Relative mean square standard deviation (RMSD) (1.8 Å), Relative mean standard Fluctuation (RMSF) (1.45 Å) and radius of gyration (4.87 Å) values of NME 3 were much lower than those of reference S4. All these confirm that our designed NME 3 is more stable than reference S4. CONCLUSION: NME 1 and NME 2 have shown better binding against wild type of EGFR. NME 3 have shown comparable binding and more stability as compared to Osimertinib against L858R/T790M/C797S mutated protein structure. The hit compound can be further explored for its Molecular mechanics with generalised Born and surface area solvation (MM-GBSA) and discrete Fourier transform (DFT) studies to find out the energy and atomic level study. In the future, this molecule could be taken for wet lab studies and can be tested for mutated EGFR inhibitory activity.

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Adulteration and substitution of medicinal plants have become a matter of great concern in recent years. Euphorbia tithymaloides is one such medicinal plant that has gained importance but is often confused with other plants of the same species. In order to address this issue, this study aimed to conduct a conventional and molecular pharmacognostic study for the identification of the root of E. tithymaloides. The root of the plant was studied for the macroscopic observations, and then, the root was ground into coarse powder for microscopic studies and to determine the physiochemical properties. The powder was subjected to extraction with solvents such as ethanol, ethanol/water (1:1), hexane, and ethyl acetate. The extracts were then used for qualitative and quantitative (phenol, alkaloids, and flavonoids) phytochemical analysis. The molecular study was performed with the DNA barcoding technique. The DNA was extracted from the root of the plant, and its purity was examined by gel electrophoresis (1% w/v). The DNA was then amplified using an Applied Biosystems 2720 thermal cycler for the rbcL, matK, and ITS primers. The amplified primers were sequenced with a 3130 Genetic Analyzer, and the generated sequences were searched for similarity in the GenBank Database using the nucleotide BLAST analysis. The micro- and macroscopic studies revealed the morphological and organoleptic characters as well as the presence of medullary rays, fiber, cork, sclereids, parenchymal cells, and scalariform vessels. The physiochemical properties were found within the limit. The phytochemical analysis revealed the presence of terpenoids, flavonoids, saponins, and alkaloids. In addition, the alkaloidal content was high in the ethanol extract (63.04 ± 3.08 mg At E/g), while the phenol content was high in the hexane extract (10.26667 ± 1.77 mg At E/g), and the flavonoid content was high in the ethyl acetate extract (41.458 ± 1.33 mg At E/g). After the BLAST analysis from the GenBank database, the rbcL, ITS, and matK primers showed a similarity percentage of 99.83, 99.84, and 100. The phylogenetic tree for the species closest to each primer was generated using the MEGA 6 software. The matK loci had the highest percentage similar to the rbcL and ITS loci, indicating that the matK loci can be used to identify the root of E. tithymaloides as a standalone. The results from this study can be used to establish a quality standard for E. tithymaloides that will ensure its quality and purity.

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Introduction: Coronavirus disease 2019 (COVID-19) pneumonia is a heterogeneous disease with variable effects on lung parenchyma, airways, and vasculature, leading to long-term effects on lung functions. Materials and Methods: This multicentric, prospective, observational, and interventional study included 1000 COVID-19 cases confirmed with reverse transcription-polymerase chain reaction. All cases were assessed with high-resolution computed tomography thorax, oxygen saturation, inflammatory marker as D-dimer at the entry point, and follow-up. Age, gender, comorbidity, use of bilevel positive airway pressure/noninvasive ventilation (BiPAP/NIV), and outcome as with or without lung fibrosis as per CT severity were key observations. In selected cases, we have performed lower limb venous Doppler and computed tomography (CT) pulmonary angiography to rule out deep-vein thrombosis (DVT) or pulmonary thromboembolism (PTE) respectively. Statistical analysis is performed by using Chi-square test. Observations and Analysis: Age (<50 and >50 years) and gender (male vs. female) has a significant association with D-dimer level (P < 0.00001 and P < 0.010, respectively). CT severity score at the entry point with the D-dimer level has a significant correlation (P < 0.00001). The D-dimer level has a significant association with the duration of illness before hospitalization (P < 0.00001). Comorbidities have a significant association with D-dimer levels (P < 0.00001). D-dimer level has a significant association with oxygen saturation (P < 0.00001). BIPAP/NIV requirement has a significant association with the D-dimer level (P < 0.00001). Timing of BIPAP/NIV requirement during hospitalization has a significant association with D-dimer level (P < 0.00001). Follow-up D-dimer titer during hospitalization as compared to normal and abnormal to entry point level has a significant association with post-COVID lung fibrosis, DVT, and PTE (P < 0.00001). Conclusions: D-dimer has documented a very crucial role in COVID-19 pneumonia in predicting the severity of illness and assessing response to treatment during hospitalization, and follow-up titers have a significant role in step-up or step-down interventions in a critical care setting.

Résumé Introducción: La neumonía por enfermedad por coronavirus 2019 (COVID 19) es una enfermedad heterogénea con efectos variables sobre el parénquima pulmonar, las vías respiratorias y la vasculatura, lo que lleva a efectos a largo plazo sobre las funciones pulmonares. Materiales y métodos: este estudio multicéntrico, prospectivo, observacional e intervencionista incluyó 1000 casos de COVID 19 confirmados con reacción en cadena de la polimerasa con transcriptasa inversa. Todos los casos fueron evaluados con tomografía computarizada de tórax de alta resolución, saturación de oxígeno, marcador inflamatorio como dímero D en el punto de entrada y seguimiento. La edad, el sexo, la comorbilidad, el uso de presión positiva en las vías respiratorias de dos niveles/ventilación no invasiva (BiPAP/NIV) y el resultado con o sin fibrosis pulmonar según la gravedad de la TC fueron observaciones clave. En casos seleccionados, hemos realizado Doppler venoso de miembros inferiores y angiografía pulmonar por tomografía computarizada (TC) para descartar trombosis venosa profunda (TVP) o tromboembolismo pulmonar (TEP) respectivamente. El análisis estadístico se realiza utilizando la prueba de Chi cuadrado. Observaciones y análisis: la edad (50 años) y el sexo (hombre vs. mujer) tienen una asociación significativa con el nivel de dímero D (P < 0,00001 y P < 0,010, respectivamente). La puntuación de gravedad de la TC en el punto de entrada con el nivel de dímero D tiene una correlación significativa (P < 0,00001). El nivel de dímero D tiene una asociación significativa con la duración de la enfermedad antes de la hospitalización (P < 0,00001). Las comorbilidades tienen una asociación significativa con los niveles de dímero D (P < 0,00001). El nivel de dímero D tiene una asociación significativa con la saturación de oxígeno (P < 0,00001). El requerimiento de BIPAP/NIV tiene una asociación significativa con el nivel de dímero D (P < 0.00001). El momento del requerimiento de BIPAP/NIV durante la hospitalización tiene una asociación significativa con el nivel de dímero D (P < 0.00001). El título de dímero D de seguimiento durante la hospitalización en comparación con el nivel normal y anormal al punto de entrada tiene una asociación significativa con la fibrosis pulmonar, la TVP y la TEP posteriores a la COVID (P < 0,00001). Conclusiones: el dímero D ha documentado un papel muy importante en la neumonía por COVID 19 para predecir la gravedad de la enfermedad y evaluar la respuesta al tratamiento durante la hospitalización, y los títulos de seguimiento tienen un papel importante en las intervenciones de aumento o reducción en un entorno de cuidados críticos. Mots-clés: Palabras clave: enfermedad por coronavirus 2019, neumonía, dímero D, trombosis venosa profunda, marcador inflamatorio, fibrosis pulmonar, embolia pulmonar.

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BACKGROUND: The tyrosine kinase epidermal growth factor receptor (TK-EGFR) has recently been identified as a useful target for anticancer treatments. The major concern for current EGFR inhibitors is resistance due to mutation, which can be overcome by combining more than one pharmacophore into a single molecule. AIM AND OBJECTIVE: In the present study, various hybrids of 1,3,4-oxadiazole-chalcone derivatives were gauged for their EGFR inhibitory potential. METHOD: The design of 1,3,4-oxadiazole-chalcone hybrid derivatives was carried out and in silico studies, viz., molecular docking, ADME, toxicity, and molecular simulation, were performed as EGFR inhibitors. Twenty-six 1,3,4-oxadiazole-chalcone hybrid derivatives were designed using the combilib tool of the V life software. AutoDock Vina software was used to perform in silico docking studies, while SwissADME and pkCSM tools were used to analyse molecules for ADME and toxicity. Desmond software was used to run the molecular simulation. RESULT: Around 50% of molecules have shown better binding affinity as compared to standard and cocrystallized ligands. CONCLUSION: Molecule 11 was found to be a lead molecule that has the highest binding affinity, good pharmacokinetics, good toxicity estimates and better protein-ligand stability.

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BACKGROUND: Past few decades have witnessed the co-existence of diabetes and hypertension leading to other health disorders. Hence, it is imperative to look into new therapies for the treatment of both hypertension and diabetes simultaneously in order to gradually reduce the pill burden and subsequent side effects. OBJECTIVE: The goal of the current work was to use several in silico methods to develop new entities that have both anti-diabetic and anti-hypertensive activity. METHODS: Structure activity relationship was drawn from the literature considering Thiazolidinones (Anti diabetes), Indole (Antihypertensive) and naturally occurring polyphenols (Dual activity) for simultaneous management of hypertension and diabetes. Fifty-six new chemical entities were designed and subjected to ADME and docking studies. Based on the Lipinski filter, bioavailability and lead likeness nineteen molecules were further docked into three PDB's (5Y2T, 4BVN, 1O8A). RESULTS: The majority of the NCE's have shown higher binding affinities than the standard drugs, with Compound 42 having the best results. Among nineteen NCE's, 50% of the compounds have shown the involvement of Thiazolidinone, Indole and Catechol pharmacophores with prominent hydrogen bonds, hydrophobic, electrostatic and pi-pi stacking interactions with all three PDB's signifying their potential dual activity. Most favourable interactions were shown by compound 42. CONCLUSION: The results obtained are encouraging for further exploration of the hit molecules for simultaneous treatment of the two diseases.

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INTRODUCTION: Cancer is the major cause of death globally. Cancer can be treated with naturally occurring Curcumin nuclei. Curcumin has a wide range of biological actions, including anti-inflammatory and anti-cancer properties. Even though it is an effective medicinal entity, it has some limitations such as instability at physiological pH and a weak pharmacokinetic profile due to the ß-diketone moiety present in it. To overcome this drawback, research was carried out on monoketone moieties in curcumin, popularly known as mono-carbonyl curcumin. OBJECTIVE: The present review focuses on different synthetic schemes and Mono-carbonyl curcumin derivative's Structure-Activity Relationship (SAR) as a cytotoxic inhibitory anticancer agent. The various synthetic schemes published by researchers were compiled. METHODS: Findings of different researchers working on mono-carbonyl curcumin as an anticancer have been reviewed, analyzed and the outcomes were summarized. RESULTS: The combination of all of these approaches serves as a one-stop solution for mono-carbonyl curcumin synthesis. The important groups on different positions of mono-carbonyl curcumin were discovered by a SAR study focused on cytotoxicity, which could be useful in the designing of its derivatives. CONCLUSION: Based on our examination of the literature, we believe that this review will help researchers design and develop powerful mono-carbonyl curcumin derivatives that can be proven essential for anticancer activity.

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Pyrimidine and Triazine are rewarding pharmacophores as seen from their presence in different naturally and synthetically occurring drug molecules. Hybridization is a functional concept used in drug design. This updated review encompasses various synthetic procedures that have been used to prepare molecular hybrids of Pyrimidine and Triazine, detailed structureactivity relationship, and molecular docking studies with patents granted. The most potent and promising hybrid compounds have also been identified. The study has revealed the synthetic feasibility of Pyrimidine-Triazine hybrids along with a plethora of potent biological activities such as anticonvulsant, antiviral, anti-inflammatory, analgesics, etc. This paper highlights the importance of coupling Pyrimidine and Triazine to provide better insight for medicinal chemists to further explore the hybrid for a significant therapeutic effect.

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Background: Chronic obstructive pulmonary disease (COPD) is a more prevalent chronic lung disease with a significant health burden, and the majority of these cases receive inadequate treatment. Methods: Prospective, observational, interview (questionnaire) based complete workup COPD study, screened 12,000 cases with chronic respiratory symptoms with cough, sputum production, and shortness of breath. A total of 6000 COPD cases were enrolled after the spirometry test. COPD cases were assessed as disease knowledge and methods of treatment offered by applying questionnaires to patients and treating physicians. Results: In the present study, 3% of study cases were aware of their COPD illness, 54% were not having knowledge about the disease, and 43% cases were not accepting the COPD diagnosis (p < 0.0001). A total of 58% of cases received inhalation treatment as levosalbutamol monotherapy in 31% cases, levosalbutamol plus beclometasone in 18% cases, and formoterol plus budesonide or salmeterol plus fluticasone only in 9% of COPD cases (p < 0.0001). Total 42% cases received oral treatment as theophylline in 16% cases, salbutamol in 7% cases, oral steroids in 19% cases (p < 0.0001). Conclusion: "Doctor-patient-drug trio" discordance clubbed as "difficult doctor, difficult patient, and difficult treatment" is a very crucial issue observed during diagnosis and management of COPD in peripheral settings in India.

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Introduction: The COVID-19 pneumonia is a heterogeneous disease with variable effect on lung parenchyma, airways, and vasculature leading to long-term effects on lung functions. Materials and methods: Multicentric, prospective, observational, and interventional study conducted during July 2020 to May 2021, in the MIMSR Medical College and Venkatesh Hospital Latur India, included 1000 COVID-19 cases confirmed with RT-PCR. All cases were assessed with lung involvement documented and categorized on HRCT thorax, oxygen saturation, inflammatory marker, ferritin at entry point, and follow-up during hospitalization. Age, gender, comorbidity, and use of BIPAP/NIV and outcome as with or without lung fibrosis as per CT severity were key observations. CT severity scoring is done as per universally accepted standard scoring tool as score < 7 as mild, 7-14 as moderate, and score > 15 as severe affection of the lung. Statistical analysis is done by using chi-square test. Observations and analysis: In study of 1000 COVID-19 pneumonia cases, age (< 50 and > 50 years) and gender (male versus female) have significant association with ferritin in predicting severity of COVID-19 pneumonia (p < 0.00001) and (p < 0.010), respectively. CT severity score at entry point with ferritin level has significant correlation in severity scores < 8, 8-15, and > 15 documented in normal and abnormal ferritin level as in 190/110, 90/210, and 40/360, respectively (p < 0.00001). Ferritin level has significant association with duration of illness, i.e., DOI < 7 days, 8-15 days, and > 15 days of onset of symptoms documented normal and abnormal ferritin levels in 30/310, 160/300, and 130/70 cases, respectively (p < 0.00001). Comorbidity as diabetes mellitus, hypertension, COPD, IHD, and obesity has significant association in COVID-19 cases with normal and abnormal ferritin level respectively (p < 0.00001). Ferritin level has significant association with oxygen saturation in COVID-19 pneumonia cases; cases with oxygen saturation > 90%, 75-90%, and < 75% are observed as normal and abnormal ferritin level in 110/100, 150/340, and 60/240 cases, respectively (p < 0.00001). BIPAP/NIV requirement during the course of COVID-19 pneumonia in critical care setting has significant association with ferritin level; cases received BIPAP/NIV during hospitalization were documented normal and abnormal ferritin level in 155/445 and 165/235 cases, respectively (p < 0.00001). Timing of BIPAP/NIV requirement during course of COVID-19 pneumonia in critical care setting has significant association with ferritin level; cases received BIPAP/NIV at entry point < 1 day, 3-7 days, and after 7 days of hospitalization were documented significance in fourfold raised ferritin level in 110/70, 150/160, and 30/80 cases, respectively (p < 0.00001). Follow-up of ferritin titer during hospitalization as compared to entry point abnormal ferritin has significant association in post-COVID lung fibrosis (p < 0.00001). Follow-up of ferritin titer during hospitalization as compared to entry point normal ferritin has significant association in post-COVID lung fibrosis (p < 0.00001). Conclusion: Ferritin is easily available, sensitive and reliable, cost-effective, and universally acceptable inflammatory marker in COVID-19 pandemic. Ferritin has very crucial role in COVID-19 pneumonia in predicting severity of illness and assessing response to treatment during hospitalization. Follow-up of ferritin titer during hospitalization and at discharge can be used as early predictor of post-COVID lung fibrosis.

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The study objective was to analyse the phytochemical constituents in aerial extracts of these plants using an HPTLC method and optimization by quality by design. Qualitative analysis of ephedrine in hydro-alcoholic extract was done via HPTLC, using a mobile phase of toluene-ethyl acetate-chloroform-formic acid in the ratio of 1:0.5:0.5:01 and the peaks were monitored at 366 nm. In the hydro-alcoholic aerial part extract, ephedrine was identified using the HPTLC method and the retardation factor (Rf) value was found to be 0.69 ± 0.01 and 0.69 ± 0.01, as compared with the standard sample. The extraction of plant materials was done using different concentration of water and alcohol solvents and quality by design was applied to optimize the extraction process and to find out the best extraction in an 80:20 ratio of hydro-alcoholic extract. In the hydro-alcoholic extract, the ephedrine was characterized using the HPTLC method and compared with the standard solution, and this method was used in herbal as well as academic research for the identification of ephedrine in poly herbal formulations as well as the ephedrine present in different plant extracts. Response surface methodology software was utilized to predict the path or choose the best extraction method. Sida rhombifolia and Sida cordifolia can be used as substitutes for Ephedra gerardiana based on the HPTLC profile.

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BACKGROUND: Entry inhibitors prevent the binding of human immunodeficiency virus protein to the chemokine receptor CXCR4 and are used along with conventional anti-HIV therapy. They aid in restoring immunity and can prevent the development of HIV-TB co-infection. AIMS: In the present study, various thiazolidinone-pyrazine derivatives earlier studied for NNRT inhibition activity were gauged for their entry inhibitor potential. OBJECTIVE: The objective of the study is to perform molecular docking, ADME, toxicity studies of some thiazolidinone-pyrazine derivatives as entry inhibitors targeting CXCR4 co-receptors. METHODS: In-silico docking studies were performed using AutoDock Vina software and compounds were further studied for ADME and toxicity using SwissADME and pkCSM software, respectively. RESULTS: Taking into consideration the docking results, pharmacokinetic behaviour and toxicity profile, four molecules (compounds 1, 9, 11, and 16) have shown potential as entry inhibitors. CONCLUSION: These compounds have shown potential as both NNRTI and entry inhibitors and hence can be used in management of immune compromised diseases like TB-HIV coinfection.

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INTRODUCTION: Cancer is reported to be one of the most life-threatening diseases. Major limitations of currently used anticancer agents are drug resistance, very small therapeutic index, and severe, multiple side effects. OBJECTIVE: The current scenario necessitates developing new anticancer agents, acting on novel targets for effectively controlling cancer. The epidermal growth factor receptor is one such target, which is being explored for 1,3,4-oxadiazole and chalcone nuclei. METHODS: Findings of different researchers working on these scaffolds have been reviewed and analyzed, and the outcomes were summarized. This review focuses on Structure-Activity Relationship studies (SARs) and computational studies of various 1,3,4-oxadiazole and chalcone hybrids/ derivatives reported as cytotoxic/EGFR-TK inhibitory anticancer activity. RESULT AND CONCLUSION: 1,3,4-oxadiazole and chalcone hybrids/derivatives with varied substitutions are found to be effective pharmacophores in obtaining potent anticancer activity. Having done a thorough literature survey, we conclude that this review will surely provide firm and better insights to the researchers to design and develop potent hybrids/derivatives that inhibit EGFR.

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A 75-year-old male presented with acute febrile respiratory illness with hypoxia and anorexia of longer duration; computed tomography (CT) of the thorax was suggestive of cavitary lung disease, with sputum smear positive for acid-fast bacilli and also having classical COVID-19 pneumonia patterns in the CT thorax; and COVID-19 rapid antigen test was positive. He was treated for COVID-19 pneumonia and antituberculosis treatment was initiated at the discharge. He was recovered of both conditions, and we have documented the crucial role of chest CT in managing this case in this pandemic period.

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BACKGROUND: Diarylquinolines like Bedaquiline have shown promising antitubercular activity by their action of Mycobacterial ATPase. OBJECTIVE: The structural features necessary for a good antitubercular activity for a series of quinoline derivatives were explored through computational chemistry tools like QSAR and combinatorial library generation. In the current study, 3-Chloro-4-(2-mercaptoquinoline-3-yl)-1- substitutedphenylazitidin-2-one derivatives have been designed and synthesized based on molecular modeling studies as anti-tubercular agents. METHODS: 2D and 3D QSAR analyses were used to designed compounds having a quinoline scaffold. The synthesized compounds were evaluated against active and dormant strains of Mycobacterium tuberculosis (MTB) H37 Ra and Mycobacterium bovis BCG. The compounds were also tested for cytotoxicity against MCF-7, A549 and Panc-1 cell lines using MTT assay. The binding affinity of designed compounds was gauged by molecular docking studies. RESULTS: Statistically significant QSAR models generated by the SA-MLR method for 2D QSAR exhibited r2 = 0.852, q2 = 0.811, whereas 3D QSAR with SA-kNN showed q2 = 0.77. The synthesized compounds exhibited MIC in the range of 1.38-14.59(µg/ml). These compounds showed some crucial interaction with MTB ATPase. CONCLUSION: The present study has shown some promising results which can be further explored for lead generation.

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