Background: A convenient and efficient methodology for the synthesis of quinazolin- 4(3H)-ones from simple and readily available 2-amino benzamides and aromatic aldehydes in ethanol using Magnesium perchlorate are being reported in the present study. Good to excellent isolated yields (68-95%) of the corresponding 2-substituted quinazolinones were obtained under mild reaction conditions with excellent functional group tolerance. The affordability of the catalyst, the wide availability of the starting materials, transition metal free synthesis and the simplicity of the procedure renders the present methodology useful in organic synthesis. Objective: A maneuver methodology developed for the synthesis of quinazolin-4(3H)-ones via using Magnesium perchlorate from 2-amino benzamides and aromatic aldehydes in ethanol. Methods: 10% mol anhydrous Magnesium perchlorate in presence of ethanol give to simply rapid formation of Quinazolin-4(3H)-ones from 1 mole of 2-amino benzamides and 1 mole of aromatic aldehydes. Results: Screening results of Anti-leishmanial showed that out of the synthesized series of 12 compounds, compounds 3c, 3d, 3g, 3h and 3i showed significant antileishmanial activities (L. donavani) with IC50 values 8.39, 9.37, 9.43, 7.1 and 8.7 μM. Conclusion: In summary, we have developed convenient synthesis of quinazolin-4(3H)-one, from simple and easily available precursor employing anhydrous Mg(ClO4)2 under green conditions.
Abstract Quinolones represent a class of potent antibacterial agents that primarily function by inhibiting bacterial topoisomerases and DNA gyrase. A crucial feature of their structure is a carboxylic acid group at the C‐3 position, which facilitates interaction with the active sites of these enzymes. Since the mid‐20th century, the emergence and proliferation of antimicrobial resistance (AMR) have posed significant challenges in society, necessitating the development of novel therapeutic agents. In this context, a new series of quinolone derivatives has been designed and synthesized based on transtorine. All synthesized compounds were tested against both Gram‐positive and Gram‐negative bacteria, as well as three fungal strains. Among the new compounds, 5a , 5d , and 5f demonstrated superior activity against Gram‐negative bacteria, with 5a showing notable effectiveness against P. aeruginosa compared to ciprofloxacin and norfloxacin. However, none of the compounds exhibited activity against fungal strains. Molecular docking studies revealed that compound 5a inhibited five bacterial proteins, primarily targeting bacterial cell wall synthesis. Additionally, ADMET parameters indicated that the promising compounds are suitable for oral administration with limited penetration across the blood–brain barrier compared to existing standards. This research indicates a potential pathway for developing new quinolone‐based antibiotics in the fight against AMR.
: In the past two decades, targeted cancer therapy has emerged as a novel class of anticancer therapeutics besides traditional chemotherapy, surgery, and radiotherapy. There is an extensive variety of anticancer drugs in the market, and several compounds are in various stages of clinical trials. Many studies indicate that these cytotoxic molecules are also associated with various types of toxicity and contrary side effects; thus, researchers all over the world are working to develop more effective and safer anticancer drugs. 1,3-thiazole derivatives have recently been identified as a novel class of cancer chemotherapeutic agents with promising activity against various tumors. In this review, we have systematically summarized and highlighted the latest developments in 1,3-thiazole derivative for anticancer activity.
Aim: This study aimed to explore the advancements, methodologies, and applications of RNA sequencing (RNA-seq) technology, emphasizing its transformative impact on genomic research. Study Design: The research involved an in-depth review of RNA-seq technology, focusing on the steps of sample preparation, sequencing, and data analysis. Place and Duration of Study: Conducted through a detailed literature review over six months, at Hygia college of Pharmacy the study sourced information from various molecular biology and genomics publications. Methodology: Advanced computational techniques were utilized to map and quantify RNA sequences, facilitating a comprehensive analysis of gene expression patterns, alternative splicing, and novel transcript discovery. High-throughput sequencing platforms like Illumina and PacBio generated extensive datasets from diverse biological samples, including tissues, single cells, and environmental microbiomes. Results: The results highlighted RNA-seq's ability to provide a high-resolution view of the transcriptome, surpassing previous technologies in both sensitivity and accuracy. RNA-seq uncovered critical insights into differential gene expression, identifying significant pathways involved in development, disease, and environmental responses. The technology also discovered numerous previously unannotated transcripts and isoforms, contributing to the expansion of existing genomic databases. Conclusion: The study concludes that RNA-seq is a crucial advancement in molecular biology, offering unprecedented insights into gene regulation and expression. Its adoption has facilitated significant breakthroughs in understanding cellular processes, disease mechanisms, and therapeutic targets. As RNA-seq technology continues to evolve, it promises to drive further innovations and applications across diverse fields in the life sciences.
Background: 3,5-Bis(arylidene)-4-piperidinones (BAP) belong to a wide class of cross conjugated dienones. The 1,5-diaryl-3-oxo-1,4-pentadienyl fragment of the BAP moiety is responsible for the molecule's anti-tumor, antioxidant, antimicrobial and anti-inflammatory manifestations. In the present study, we present combinations of phosphonate and 3,5-bis(arylidene)-4- piperidone pharmacophores. The anti-inflammatory, anti-oxidant potential, anti-proliferative, cytotoxic potential and antimicrobial of the title compounds were evaluated in in-vitro bioassay paradigms. Methods: A novel class of phosphonate linked 3,5-Bis(aryl methylene)-4-piperidone derivatives were synthesized from simple, versitalie and efficient synthetic methodology. All of the synthesized compounds were screened for their in vitro anti-inflammatory, in vitro anti-oxidant potential, in vitro anti-proliferative, in vitro cytotoxic potential and in vitro antimicrobial activity. Amongst all the synthesized compounds in series, phosphonate derivatives of 3,5-Bis(arylmethylene)-4- piperidone containing 4-hydroxy-3-methoxyphenyl curcumin like prototype were more active than phenyl substituted compounds. Results: The results of the screening revealed that compounds 5e, 5f, 5g, 5h were more active candidates as compared to 5a, 5b, 5c and 5d, however 5d can be readily endorsed as the most active compound of the series. Structure- activity relationship of the synthesized series suggested that structural resemblance of the synthesized compounds with that of curcumin was enormously accountable for the compounds anti-inflammatory, antioxidant and cytotoxic potential activity. Conclusion: The in-vitro biological spectrum indicated that the substitution of groups at third and fourth position and alkyl phosphonates substitution potentiates the activity as compared to curcumin.
Eribulin mesylate is the latest addition in the armamentarium of management of metastatic breast cancer (MBC) with a unique mechanism of action. Although the multicentric EMBRACE trial suggests significant overall survival benefit from this novel drug, its effectiveness in Indian population is yet to be evaluated.Presented here is a single center experience of eight patients who were administered eribulin for MBC. Patients had received a median of 3 prior chemotherapies before eribulin administration. The median dose of eribulin therapy was 5 cycles (range: 2-6 cycles).The objective response rate was 75% (CR in one and PR in five out of eight patients). Response was seen across all subtypes of patients. Eribulin was well tolerated. No serious adverse events were reported.Eribulin conferred good response rates with satisfactory tolerability profile in Indian patients. Its use in earlier lines and in combination with other drugs may achieve deeper and longer responses.
Objectives: In the current study, we report the synthesis, characterization and neuropharmacology of quinalozinones tethered with aromatic (3a- 3i) and heteroaromatic substitution (3j, 3k and 3l) as effective anxiolytic agents. Background: Anxiety and depression are often co-morbid with neurological as well as other medical maladies. Clinically popular anxiolytics (Benzodiazepines) are accompanied by untoward sedation and other CNS depressive actions. The quinazolinone moiety is a privileged pharmacophore with a wide pharmacological spectrum. we herein report the synthesis, characterization and pharmacological evaluation of some 2-substituted quinazolinone derivatives. Methods: The synthesized compounds were characterized using 1H-NMR and TLC analysis. Behavioral analysis was performed using EPM, OFT, PIST and FST bioassay. For further justifying the therapeutic claim, we performed systemic and neurotoxicological analysis of the most potent members of the series using OECD mandated protocols. The studies advocated the compounds to have a wide therapeutic window with >1000mg/kg and >500mg/kg LD50 and NOAEL respectively. Results: The compounds with an electronegative group in the quinazolinone nucleus (3f, 3e, 3d and 3c) induces anxiolysis devoid of sedative adverse reaction. In addition, Anti-depressant efficacy of 3f, 3e, 3d and 3c observed in rodents is a result of decrease in anxiety level. It has been found that Neurotoxicology of the potent members (3f, 3e, 3d and 3c) advocates their wide therapeutic window with >1000mg/kg LD50 and >5000mg/kg NOAEL. Conclusion: Our findings in behavioral bioassays reveal that inducing an electronegative group into the Quinazolinone nucleus yields the most potent members of the series (3f, 3e, 3d and 3c). The said compounds were found to render anxiolysis and anti-depressive action without sedative-hypnotic side effects in rodent models. In summary, we state that extending the studies in clinical setting would furbish the contours of current anxiolytic therapy especially in anxiety co morbid with medical maladies.
AbstractAfter the pandemic COVID-19, global health agencies remind us that tuberculosis is the deadliest infectious disease worldwide. As per WHO reports, approximately ten million people are infected with tuberculosis every year. Only a small portion of global cases receive imperative life-saving medicines. Even in the face of enduring efforts in the discovery of effective management of tuberculosis, the disease remains to affect millions of patients worldwide, with a high rate of morbidity and mortality. Considering the low treatment success, high drug treatment failure, and resistance to existing antituberculosis drugs, there is an urgency for the development of new chemical entities as antituberculosis agents. The development of resistance in tuberculosis (TB) patients to the medications used to treat and prevent the disease presents a significant challenge worldwide. Extensive research confines the molecules to counteract this disease has led to identifying many inhibitory pharmacophores. A wide range of compounds has been screened to find a novel ideal drug candidate for curing tuberculosis. Chalcone and its derivatives are considered precursors of flavonoids and isoflavonoids and display a diverse array of reported pharmacological activities including anti-inflammatory and antituberculosis activities. As this field continues to evolve, these molecules present further opportunities for understanding the mechanism of antituberculosis action and the treatment of MDR. Here, we summarize the impact of chalcone derivatives in tuberculosis treatment. The current statuses of various synthetic chalcone-based approaches for tuberculosis treatment are systematically reviewed here.Keywords: TuberculosisMDRflavonoidschalconesanti-infective agents AcknowledgmentsThe authors thank SGT College of Pharmacy, Shree Guru Gobind Singh Tricentenary (SGT) University, Gurugram, Haryana India for technical support.Disclosure statementThe authors declared no conflict of interest.
In the last decade, there has been immense growth in research activities related to tribology. Tribology can have a big impact on the needs of industries to reduce losses and waste by developing new tribological components and materials. Hence, there is a strong connection between tribology and the fourth industrial revolution, i.e., industry 4.0. Tribology is a multidisciplinary field, and the results of research in the field of tribology are widely spread among various disciplines. This review paper briefs the recent advances in various research areas in tribology covering surface engineering, wear and lubrication. The main objective of this review is to summarize the new aspects in the field of tribology, like the numerical techniques of lubrication to model new lubrication schemes, solid superlubricity, superlubricity at the microscopic scale, superlubricity with coating and new 2D materials. The direction for future research in the field has been highlighted. The paper will be beneficial for researchers working in the field of tribology.
Abstract: The signal transduction and cell proliferation are regulated by the epidermal growth factor receptor. The proliferation of tumor cells, apoptosis, invasion, and angiogenesis is inhibited by the epidermal growth factor receptor. Thus, breast cancer, non-small cell lung cancer, cervical cancer, glioma, and bladder cancer can be treated by targeting the epidermal growth factor receptor. Although third-generation epidermal growth factor receptor inhibitors are potent drugs, patients exhibit drug resistance after treatment. Thus, the search for new drugs is being continued. Among the different potent epidermal growth factor receptor inhibitors, we have reviewed the indole-based inhibitors. We have discussed the structure-activity relationship of the compounds with the active sites of the epidermal growth factor receptor receptors, their synthesis, and molecular docking studies.
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