Novel quinolone substituted 1,3,4-oxadiazole derivatives: design, synthesis, antimicrobial and anti-inflammatory potential.

A novel series of quinolone-substituted 1,3,4-oxadiazole derivatives 4(a-l) have been designed and synthesized. The target compounds were investigated for their antibacterial activity against gram positive (Staphylococcus aureus, ATCC 25923, Enterococcus faecalis, ATCC 29212) and gram negative bacterium (Escherichia coli, ATCC 25922, Pseudomonas aeruginosa, ATCC 27853) for antifungal activity using (Candida albicans, ATCC 10231) and anti-inflammatory activity as COX-II inhibitors, respectively. The 1,3,4-oxadiazole functionality was introduced at C-6 position of pipemidic acid derivatives. IR, 1H NMR and Mass spectrometry techniques confirmed the structure of synthesized derivatives. The quinolone (pipemidic acid)-oxadiazole hybrid derivatives were effective against bacterial strains. When compared to ciprofloxacin (MIC 16 µg/mL), the compounds under consideration (4f, 4h, and 4k) showed significant antibacterial activity against all bacterial strains except Enterococcus faecalis, with MICs of 8 µg/mL. On the other hand, synthesized target compounds 4(a-l) did not respond well against Candida albicans fungal strain. The compound (4k) represents high % inhibition against COX-II. The compounds (4f, 4h and 4k) exhibited highest hydrogen bonding interaction with ARG57, ARG72, ARG78, LEU54 and MET16 target residues with a binding energy of - 8.4, - 8.6 and - 8.5 kcal/mol into the active pocket of DNA gyrase enzyme respectively even better in comparison to reference ligands. Based on the docking study, quinolone (pipemidic acid) oxadiazole hybrid structural ligands exhibited strong interaction at binding pockets of DNA gyrase enzyme.

Eco-friendly Regioselective Synthesis, Biological Evaluation of Some New 5-acylfunctionalized 2-(1H-pyrazol-1-yl)thiazoles as Potential Antimicrobial and Anthelmintic Agents.

The present study describes an eco-friendly NBS-assisted regioselective synthesis of new 5-acylfunctionalized 5-acylfunctionalized 2-(1H-pyrazol-1-yl)thiazoles by condensation of 3,5-dimethyl-1H-pyrazole-1-carbothioamide with unsymmetrical 1,3-diketones under solvent-free conditions. The structural elucidation of the newly synthesized compounds was accomplished using various spectroscopic techniques viz. FTIR, NMR and mass spectrometry. All the newly synthesized compounds were examined for their in vitro antimicrobial potential against both pathogenic gram positive and gram negative bacterial and fungal species as well as anthelmintic activity against Pheretima posthuma earthworms. The results of antimicrobial activity revealed that all tested compounds 3 a-j showed excellent antimicrobial potential particularly against S. aureus. It was also observed that compounds 3 e and 3 i (MIC=62.5 µg/mL) showed greater potency against E. coli, whereas compounds 3 a and 3 h (MIC=50 µg/mL and 62.5 µg/mL) demonstrated better activity against P. aeruginosa and compound 3 i (MIC=62.5 µg/mL) exhibited superior activity against S. pyogenus when compared to standard drug Ampicillin (MIC=100µg/mL). Compound 3 e and 3 j revealed remarkable antifungal and anthelmintic activities. To find out binding interactions of target compounds with target proteins and pharmacokinetic parameters of the compounds, in silico investigations involving molecular docking studies and ADMET predictions were also performed.

Designing a Conserved Immunogenic Peptide Construct from the Nucleocapsid Protein of Puumala orthohantavirus.

Puumala orthohantavirus (PUUV) is an emerging zoonotic virus endemic to Europe and Russia that causes nephropathia epidemica, a mild form of hemorrhagic fever with renal syndrome (HFRS). There are limited options for treatment and diagnosis of orthohantavirus infection, making the search for potential immunogenic candidates crucial. In the present work, various bioinformatics tools were employed to design conserved immunogenic peptides containing multiple epitopes of PUUV nucleocapsid protein. Eleven conserved peptides (90% conservancy) of the PUUV nucleocapsid protein were identified. Three conserved peptides containing multiple T and B cell epitopes were selected using a consensus epitope prediction algorithm. Molecular docking using the HPEP dock server demonstrated strong binding interactions between the epitopes and HLA molecules (ten alleles for each class I and II HLA). Moreover, an analysis of population coverage using the IEDB database revealed that the identified peptides have over 90% average population coverage across six continents. Molecular docking and simulation analysis reveal a stable interaction with peptide constructs of chosen immunogenic peptides and Toll-like receptor-4. These computational analyses demonstrate selected peptides' immunogenic potential, which needs to be validated in different experimental systems.

Fate, source apportionment and fractionation of potentially toxic elements in agricultural soil around a densely populated, semiarid urban center of India: baseline study and ecological risk assessment.

This study is on the outskirts of the rapidly growing city of Jaipur, located in the semiarid region of India and gateway to the 'Great Indian Thar' desert, and focused on potentially toxic elements (PTE) pollution in the farmlands around the city. Concentrations of PTE, along with associated soil parameters such as pH, available nitrogen, organic carbon, phosphorus, and potassium, were estimated in agricultural soil samples near an industrial region on the outskirts of the capital city of the largest state of India. The PTE concentrations in the soil were in the following order: Mn > Pb > Ni > Cr > Cu > Cd. Soil pollution indices, such as the geochemical accumulation index (Igeo), contamination factor (CF), and ecological risk index (ERI), indicated that the soil was moderately to highly polluted. The result of BCR extraction techniques showed Cd is found mainly in the exchangeable and residual fractions, Pb, Mn were found in the reducible as well as residual fractions, while other PTE were mostly bound to residual fraction. All other PTEs are primarily found in the residual fraction, tightly linked with the silicate lattice of soil minerals. Multivariate analysis and the Pearson correlation matrix indicate a common source apportionment for Pb and Cd. Cd, and Pb concentrations in agricultural soil indicate ecological harm that warrants immediate attention and policy-level intervention.

Cross-reactivity of hantavirus antibodies after immunization with PUUV antigens.

Nephropathia epidemica (NE), caused by Puumala (PUUV) orthohantavirus, is endemic in the Republic of Tatarstan (RT). There are limited options for NE prevention in RT. Currently, available vaccines are made using Haantan (HNTV) orthohantavirus antigens. In this study, the efficacy of microvesicles (MVs) loaded with PUUV antigens to induce the humoral immune response in small mammals was analyzed. Additionally, the cross-reactivity of serum from immunized small mammals and NE patients with HNTV, Dobrava, and Andes orthohantaviruses was investigated using nucleocapsid (N) protein peptide libraries. Finally, the selected peptides were analyzed for allergenicity, their ability to induce an autoimmune response, and their interaction with Class II HLA. Several N protein peptides were found to be cross-reactive with serum from MVs immunized small mammals. These cross-reactive epitopes were located in oligomerization perinuclear targeting and Daxx-interacting domains. Most cross-reactive peptides lack allergenic and autoimmune reactivity. Molecular docking revealed two cross-reacting peptides, N6 and N19, to have good binding with three Class II HLA alleles. These peptides could be candidates for developing vaccines and therapeutics for NE.

Synergistic microwave and acidic deep eutectic solvent-based pretreatment of Theobroma cacao pod husk biomass for xylooligosaccharides production.

The bioconversion of lignocellulosic biomass into novel bioproducts is crucial for sustainable biorefineries, providing an integrated solution for circular economy objectives. The current study investigated a novel microwave-assisted acidic deep eutectic solvent (DES) pretreatment of waste cocoa pod husk (CPH) biomass to extract xylooligosaccharides (XOS). The sequential DES (choline chloride/citric acid, molar ratio 1:1) and microwave (450W) pretreatment of CPH biomass was effective in 67.3% xylan removal with a 52% XOS yield from total xylan. Among different XOS of varying degrees of polymerization, a higher xylobiose content corresponding to 69.3% of the total XOS (68.22 mg/g CPH) from liquid fraction was observed. Enzymatic hydrolysis of residual xylan from pretreated CPH biomass with low commercial xylanase (10 IU/g) concentration yielded 24.2% XOS. The MW-ChCl/citric acid synergistic pretreatment approach holds great promise for developing a cost-effective and environmentally friendly method contributing to the sustainable production of XOS from agricultural waste streams.

Quinolone scaffolds as potential drug candidates against infectious microbes: a review.

Prevalence of microbial infections and new rising pathogens are signified as causative agent for variety of serious and lethal health crisis in past years. Despite medical advances, bacterial and fungal infections continue to be a rising problem in the health care system. As more bacteria develop resistance to antibiotics used in therapy, and as more invasive microbial species develop resistance to conventional antimicrobial drugs. Relevant published publications from the last two decades, up to 2024, were systematically retrieved from the MEDLINE/PubMed, SCOPUS, EMBASE, and WOS databases using keywords such as quinolones, anti-infective, antibacterial, antimicrobial resistance and patents on quinolone derivatives. With an approach of considerable interest towards novel heterocyclic derivatives as novel anti-infective agents, researchers have explored these as essential tools in vistas of drug design and development. Among heterocycles, quinolones have been regarded extremely essential for the development of novel derivatives, even able to tackle the associated resistance issues. The quinolone scaffold with its bicyclic structure and specific functional groups such as the carbonyl and acidic groups, is indeed considered a valuable functionalities for further lead generation and optimization in drug discovery. Besides, the substitution at N-1, C-3 and C-7 positions also subjected to be having a significant role in anti-infective potential. In this article, we intend to highlight recent quinolone derivatives based on the SAR approach and anti-infective potential such as antibacterial, antifungal, antimalarial, antitubercular, antitrypanosomal and antiviral activities. Moreover, some recent patents granted on quinolone-containing derivatives as anti-infective agents have also been highlighted in tabular form. Due consideration of this, future research in this scaffold is expected to be useful for aspiring scientists to get pharmacologically significant leads.

A systematic review of EEG based automated schizophrenia classification through machine learning and deep learning.

The electroencephalogram (EEG) serves as an essential tool in exploring brain activity and holds particular importance in the field of mental health research. This review paper examines the application of artificial intelligence (AI), encompassing machine learning (ML) and deep learning (DL), for classifying schizophrenia (SCZ) through EEG. It includes a thorough literature review that addresses the difficulties, methodologies, and discoveries in this field. ML approaches utilize conventional models like Support Vector Machines and Decision Trees, which are interpretable and effective with smaller data sets. In contrast, DL techniques, which use neural networks such as convolutional neural networks (CNNs) and long short-term memory networks (LSTMs), are more adaptable to intricate EEG patterns but require significant data and computational power. Both ML and DL face challenges concerning data quality and ethical issues. This paper underscores the importance of integrating various techniques to enhance schizophrenia diagnosis and highlights AI's potential role in this process. It also acknowledges the necessity for collaborative and ethically informed approaches in the automated classification of SCZ using AI.

A Profound Insight into the Structure-activity Relationship of Ubiquitous Scaffold Piperazine: An Explicative Review.

Despite extensive research in the field of drug discovery and development, still there is a need to develop novel molecular entities. Literature reveals a substantial heterocyclic nucleus named, piperazine, which shows an immense therapeutic voyage. For several decades, molecules having the piperazine nucleus have entered the market as a drug exhibiting biological potential. It was known to possess antipsychotic, antihistamine, antianginal, antidepressant, anticancer, antiviral, cardioprotective, and anti-inflammatory activity with a specific basis for structural activity relationship. Thus, it is regarded as a key structural feature in most of the already available therapeutic drugs in the market. Reports also suggest that the extensive utilization of these currently available drugs having a piperazine nucleus shows increasing tolerance significantly day by day. In addition to this, various other factors like solubility, low bioavailability, cost-effectiveness, and imbalance between pharmacokinetics and pharmacodynamics profile limit their utilization. Focusing on that issues, various structural modification studies were performed on the piperazine moiety to develop new derivatives/analogs to overcome the problems associated with available marketed drugs. Thus, this review article aims to gain insight into the number of structural modifications at the N-1 and N-4 positions of the piperazine scaffold. This SAR approach may prove to be the best way to overcome the above-discussed drawbacks and lead to the design of drug molecules with better efficacy and affinity. Hence, there is an urgent need to focus on the structural features of this scaffold which paves further work for deeper exploration and may help medicinal chemists as well as pharmaceutical industries.

PAS Dimerization at the Nexus of the Mammalian Circadian Clock.

Circadian rhythms are genetically encoded molecular clocks for internal biological timekeeping. Organisms from single-cell bacteria to humans use these clocks to adapt to the external environment and synchronize their physiology and behavior to solar light/dark cycles. Although the proteins that constitute the molecular 'cogs' and give rise to circadian rhythms are now known, we still lack a detailed understanding of how these proteins interact to generate and sustain the ∼24-hour circadian clock. Structural studies have helped to expand the architecture of clock proteins and have revealed the abundance of the only well-defined structured regions in the mammalian clock called Per-ARNT-Sim (PAS) domains. PAS domains are modular, evolutionarily conserved sensory and signaling domains that typically mediate protein-protein interactions. In the mammalian circadian clock, PAS domains modulate homo and heterodimerization of several core clock proteins that assemble into transcription factors or repressors. This review will focus on the functional importance of the PAS domains in the circadian clock from a biophysical and biochemical standpoint and describe their roles in clock protein interactions and circadian timekeeping.

Comparative evaluation of milk proteins and oil-seed-cake-derived proteins extracted by chemical and biological methods for obesity management.

BACKGROUND: In light of the exponential rise in global population, there is a critical requirement to reduce food waste on a global scale. According to studies, agricultural wastes such as oil-seed cakes offer great nutritional value. Acid precipitation (A) and alkaline extraction methods (traditional methods) were used to extract protein from oil-seed cakes; however, both procedures are linked to decreased protein quality and quantity, which prompted the development of a novel strategy known as the biological/microbial/probiotic (B) method. Therefore, the present study aimed to highlight the optimal way of protein extraction from oil-seed cakes and the effect of extraction methods on protein efficacy against obesity. The outcomes were also compared with milk proteins. RESULTS: In vitro study provided evidence that proteins from both sources (plant and milk) suppressed adipogenesis and stimulated adipolysis in 3T3L-1 cells. For the in vivo study, mice were fed with different protein extracts: soya protein preparation (SPP), ground protein preparation (GPP), whey protein (WP) and casein protein (CP) containing 40% of their calories as fat. Body weight decreased significantly in all the rats except CP-fed rats. Body mass index, atherogenic index, plasma triglyceride and very-low-density lipoprotein cholesterol level decreased significantly in all the groups in comparison to the model group (high-fat-diet group), but the decrease was more pronounced in plant proteins than milk proteins. In hepatocytes, the expression of fasting-induced adipose factor, carnitine palmitoyltransferase I and peroxisome proliferator-activated receptor α genes was increased significantly in SPP-fed groups. Adiponectin gene expression was upregulated significantly in visceral fat tissue in groups fed SPP-B, GPP-A and CP, whereas leptin gene was downregulated significantly in all groups except SPP-A. CONCLUSION: This study demonstrates that SPP-B showed the most effective anti-obesity property, followed by WP. Additionally, we found that the biological precipitation approach produced better outcomes for plant proteins isolated from oil-seed cakes than the acid precipitation method. © 2023 Society of Chemical Industry.

From Plants to Therapies: Exploring the Pharmacology of Coumestrol for Neurological Conditions.

Neurological disorders are possibly the most prevalent and have been identified to occur among individuals with autism beyond chance. These disorders encompass a diverse range of consequences with neurological causes and have been regarded as a major threat to public mental health. There is no tried-and-true approach for completely protecting the nervous system. Therefore, plant-derived compounds have developed significantly nowadays. Coumestrol (CML) is a potent isoflavone phytoestrogen with a protective effect against neurological dysfunction and has been discovered to be structurally and functionally similar to estrogen. In recent years, more research has been undertaken on phytoestrogens. This research demonstrates the biological complexity of phytoestrogens, which consist of multiple chemical families and function in various ways. This review aimed to explore recent findings on the most significant pharmacological advantages of CML by emphasising neurological benefits. Numerous CML extraction strategies and their pharmacological effects on various neurological disorders, including PD, AD, HD, anxiety, and cognitive impairments, were also documented.

Women's awareness of perinatal mental health conditions and the acceptability of being asked about mental health in two regions in India: a qualitative study.

BACKGROUND: Mental health conditions are common during pregnancy and the first year after childbirth. Early detection allows timely support and treatment to be offered, but identifying perinatal mental health conditions may be challenging due to stigma and under-recognition of symptoms. Asking about symptoms of mental health conditions during routine antenatal and postnatal appointments can help to identify women at risk. This study explores women's awareness of perinatal mental health conditions, their views on the acceptability of being asked about mental health and any preference for specific assessment tools in two regions in India. METHODS: Focus group discussions (FGDs) were conducted with pregnant, post-partum and non-perinatal women in Kangra, Himachal Pradesh (northern India) and Bengaluru, Karnataka (southern India). Settings included a hospital antenatal clinic and obstetric ward, Anganwadi Centres and Primary Health Centres. FGDs were facilitated, audio-recorded and transcribed. Narratives were coded for emerging themes and analysed using thematic analysis. RESULTS: Seven FGDs including 36 participants were conducted. Emerging themes were: manifestations of and contributors to mental health conditions; challenges in talking about mental health; and the acceptability of being asked about mental health. Difficult familial relationships, prioritising the needs of others and pressure to have a male infant were cited as key stressors. Being asked about mental health was generally reported to be acceptable, though some women felt uncomfortable with questions about suicidality. No preference for any specific assessment tool was reported. CONCLUSIONS: Women face many stressors during the perinatal period including difficult familial relationships and societal pressure to bear a male infant. Being asked about mental health was generally considered to be acceptable, but questions relating to suicidality may be challenging in a community setting, requiring sensitivity by the interviewer. Future studies should assess the acceptability of mental health assessments in 'real world' antenatal and postnatal clinics and explore ways of overcoming the associated challenges in resource-constrained settings.

Insights into the recent advances of agro-industrial waste valorization for sustainable biogas production.

Recent years have seen a transition to a sustainable circular economy model that uses agro-industrial waste biomass waste to produce energy while reducing trash and greenhouse gas emissions. Biogas production from lignocellulosic biomass (LCB) is an alternative option in the hunt for clean and renewable fuels. Different approaches are employed to transform the LCB to biogas, including pretreatment, anaerobic digestion (AD), and biogas upgradation to biomethane. To maintain process stability and improve AD performance, machine learning (ML) tools are being applied in real-time monitoring, predicting, and optimizing the biogas production process. An environmental life cycle assessment approach for biogas production systems is essential to calculate greenhouse gas emissions. The current review presents a detailed overview of the utilization of agro-waste for sustainable biogas production. Different methods of waste biomass processing and valorization are discussed that contribute towards developing an efficient agro-waste to biogas-based circular economy.

Chemical Diversity and Medicinal Potential of Vitex negundo L.: From Traditional Knowledge to Modern Clinical Trials.

BACKGROUND: In Vedic context, Nirgundi (V. negundo) has been utilized for its anti-inflammatory, analgesic, and wound-healing properties. It has been employed to alleviate pain, treat skin conditions, and address various ailments. The plant's leaves, roots, and seeds have all found applications in traditional remedies. The knowledge of Nirgundi's medicinal benefits has been passed down through generations, and it continues to be a part of Ayurvedic and traditional medicine practices in India.

Mutation spectrum and enzyme profiling of G6PD deficiency in neonates of north India: a prospective study.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked disorder with well-established clinical and allelic heterogeneity and ethnic disparity. With ~390,000 annual births with G6PD deficiency in India, it emerges as the most predictable and preventable inbornmetabolic error. Disease prevalence and mutation spectrum have been reasonably reported fromcentral, western and southern parts of India and are mostly retrospective studies.Although prevalence data fromnorth India is available, there is paucity of data on the mutation spectrum and genotype-phenotype correlation (GxP). Thus, we aimed at establishing the clinical and mutation profiles for G6PD, as a part of a large prospective newborn screening study conducted between 2014 and 2016 across hospitals in Delhi, India. G6PD activity levels were measured at 24-48 h of life for ~200,000 neonates using Victor 2D and/or Genomic Screening Processor followed by confirmatory spectrophotometric analysis usingRBClysates of the respective neonates based on clinical symptoms.Asubset of 570 enzyme deficient neonates were screened formutations by polymerase chain reaction-restriction fragment length polymorphismand/or Sanger sequencing.Mediterraneanwas the most common mutation (n=318; 55.8%) with the lowest enzyme activity and most severe phenotype, followed by G6PD Orissa (n=187;32.8%); Kerala-Kalyan (n=25); Jammu (n=24);Mahidol (n=14); Chattam(n=1) andNilgiri/Coimbra (n=1).Of the 163 intramural neonates followed up, 68 developed clinical jaundice. However, no correlation was observed between jaundice and enzyme level. Notable outcome of this first ever prospective screening approach for G6PD deficiency in neonates may help in prediction of disease severity and appropriate timely management.

Pharmacological modulation of HIF-1 in the treatment of neuropsychiatric disorders.

Hypoxia-inducible factor 1 has been identified as an important therapeutic target in psychiatric illnesses. Hypoxia is a condition in which tissues do not receive enough oxygen, resulting in less oxidative energy production. HIF-1, the master regulator of molecular response to hypoxia, is destabilized when oxygen levels fall. HIF-1, when activated, increases the gene transcription factors that promote adaptive response and longevity in hypoxia. HIF-regulated genes encode proteins involved in cell survival, energy metabolism, angiogenesis, erythropoiesis, and vasomotor control. Multiple genetic and environmental variables contribute to the pathophysiology of psychiatric disease. This review focuses on the most recent findings indicating the role of oxygen deprivation in CNS damage, with strong attention on HIF-mediated pathways. Several pieces of evidence suggested that, in the case of hypoxia, induction and maintenance of HIF-1 target genes may help reduce nerve damage. Major new insights into the molecular mechanisms that control HIF's sensitivity to oxygen are used to make drugs that can change the way HIF works as a therapeutic target for some CNS diseases.

Recent advances in synthetic strategies and SAR of thiazolidin-4-one containing molecules in cancer therapeutics.

Cancer is one of the life-threatening diseases accountable for millions of demises globally. The inadequate effectiveness of the existing chemotherapy and its harmful effects has resulted in the necessity of developing innovative anticancer agents. Thiazolidin-4-one scaffold is among the most important chemical skeletons that illustrate anticancer activity. Thiazolidin-4-one derivatives have been the subject of extensive research and current scientific literature reveals that these compounds have shown significant anticancer activities. This manuscript is an earnest attempt to review novel thiazolidin-4-one derivatives demonstrating considerable potential as anticancer agents along with a brief discussion of medicinal chemistry-related aspects of these compounds and structural activity relationship studies in order to develop possible multi-target enzyme inhibitors. Most recently, various synthetic strategies have been developed by researchers to get various thiazolidin-4-one derivatives. In this review, the authors highlight the various synthetic, green, and nanomaterial-based synthesis routes of thiazolidin-4-ones as well as their role in anticancer activity by inhibition of various enzymes and cell lines. The detailed description of the existing modern standards in the field presented in this article may be interesting and beneficial to the scientists for further exploration of these heterocyclic compounds as possible anticancer agents.