Current Topics in Medicinal Chemistry - Volume 22, Issue 10, 2022

Recently, there has been great progress in the field of extremely sensitive and precise detection of bioanalytes. The importance of the utilization of nanoparticles in biosensors has been recognized due to their unique properties. Specifically, nanoparticles of gold, silver, and magnetic plus graphene, quantum dots, and nanotubes of carbon are being keenly considered for utilization within biosensors to detect nucleic acids, glucose, or pathogens (bacteria as well as a virus). Taking advantage of nanoparticles, faster and sensitive biosensors can be developed. Here, we review the nanoparticles' contribution to the biosensors field and their potential applications.

Copper is the third most common heavy metal and an indispensable component of life. Variations of body copper levels, both structural and cellular, are related to a number of disorders; consequently, the pathophysiological importance of copper ions demands the development of sensitivity and selection for detecting these organisms in biological systems. In recent years, the area of fluorescent sensors for detecting copper metal ions has seen revolutionary advances. Consequently, closely related fields have raised awareness of several diseases linked to copper fluctuations. Further developments in this field of analysis could pave the way for new and innovative treatments to combat these diseases. This review reports on recent progress in the advancement of three fields of fluorescent probes; chemodosimeters, near IR fluorescent probes, and ratiometric fluorescent probes. Methods used to develop these fluorescent probes and the mechanisms that govern their reaction to specific analytes and their applications in studying biological systems, are also given.

Background: Breast carcinomas aka triple-negative breast cancers (TNBC) are one of the most complex and aggressive forms of cancers in females. Recently, studies have shown that these carcinomas are resistant to hormone-targeted therapies, which makes it a priority to search for effective and potential anticancer drugs. The present study aimed to synthesize and develop the 2Dquantitative structural activity relationship model (QSAR) of quinoxaline derivatives as a potential anticancer agent. Methods: Quinoxaline derivatives were designed and synthesized (8a-8i and 9a-9d) and the 2DQSAR model against TNBC was developed using VLife MDS v4.4. The anticancer activity was investigated against the TNBC MDA-MB-231 cell line using an MTT cytotoxicity assay. Molecular docking studies along with the estimation of ADMET parameters were done using Discovery Studio. The most potent compound was docked against the β-tubulin protein target (PDB: 4O2B), using the Autodock Vina v0.8 program. Results: Eleven derivatives of quinoxaline were designed and synthesized (8a-8i and 9a-9d) and a 2D-QSAR model was developed against the TNBC MDA-MB231 cell line. The regression coefficient values for the training set were (r²) 0.78 and (q²) 0.71. Further, external test set regression (pred_r²) was 0.68. Five molecular descriptors viz., energy dispersive (Epsilon3), protein-coding gene (T_T_C_6), molecular force field (MMFF_6), most hydrophobic hydrophilic distance (XA), and Zcomp Dipole were identified. After ADMET, the best analog 8a showed the best activity against the TNBC cell line. The best-predicted hit '8a' was found to bind within the active site of the β- tubulin protein target. Conclusion: The newly synthesized quinoxaline compounds could serve as potent leads for the development of novel anti-cancer agents against TNBC.

Background: Solanum pubescens Willd, growing wild in the hills of Rayadurg jurisdiction of Southwestern Andhra Pradesh, has gained significant attention among researchers for its diverse folkloric applications, existence of novel phytochemicals and leaf extracts which hold great medicinal promises. To date, the S. pubescens fruit’s essential oil (SPO) has never been investigated. Methods: The current research has been focused to evaluate the chemical composition of S. pubescens fruit essential oil through Gas Chromatography-Mass Spectrometry (GC-MS), followed by the investigation of antibacterial, antifungal, anti-inflammatory, analgesic and wound healing activities in appropriate models to uncover its biological potentials. Extraction of (Solanopuboil/SPO) from the fresh unripe fruits of Solanum pubescens was carried out in Buchner funnel and Whatman no.10 filter paper and concentrated at 40°C using a rotary evaporator. The metabolic profiling of SPO was analysed by GC-MS technique. The MIC, MBC, activity index, and total antimicrobial activity of SPO were evaluated using standard procedures. Anti-inflammatory activity of SPO was screened using Carrageenan induced paw oedema and Cotton pellet-induced granuloma. Tail immersion test, Acetic acid writhing response and Formalin paw lick test was performed in rats in order to examine the analgesic activity of SPO. Wound healing activity of SPO was investigated by performing the incision wound model, Excision wound model and Dead space wound model in rats. Results: The SPO displayed a constant degree of antimicrobial activity against B. cereus, B. subtilis, E. coli, A. niger, A. fumigatus and C. albicans with significant anti-inflammatory and analgesic activities. Also, a prominent wound healing potential of it was observed in excision, incision and dead space wound models with considerable elevation in granulation tissue hydroxyproline, hexuronic acid and hexosamine content in association with remarkable regulation of anti-inflammatory and antioxidant markers i.e., Lipid peroxidase (LPO), Nitric Oxide (NO), Superoxide dismutase (SOD), Glutathione (GSH), Catalase (CAT), Glutathione Peroxidase (GPx). Conclusion: These findings strongly validate the therapeutic potential of S. pubescens fruit essential oil in antimicrobial and anti-inflammatory mediated wound healing and suggests its promising application as valuable and novel indigenous leads in the food and pharmaceutical industries. To the best of our knowledge, this is the first-ever investigatory report on the systematic phytochemical and therapeutic examination of S. pubescens fruit essential oil.

Introduction: Selonsertib, the most recently developed selective inhibitor of apoptosis signal-regulating kinase 1. We elucidated the binding characteristics, mechanism of interaction, and dynamic behaviors of selonsertib with human serum albumin (HSA), a major circulatory transport protein. Methods: Different biophysical approaches (fluorescence quenching and isothermal titration calorimetry (ITC) were combined with various in silico techniques to examine the binding of selonsertib to HSA. Molecular docking results, analysis of molecular dynamics trajectories, and essential dynamics investigations indicated the stable binding of selonsertib to HSA. Further in vitro studies were performed to validate the observed interaction. Results: ITC results confirmed the robust binding and high affinity of selonsertib and HSA. Likewise, the fluorescence quenching results highlighted the binding affinity of selonsertib and HSA. Collectively, our findings offer deeper insight into the binding mechanism of selonsertib and HSA, emphasizing the selonsertib-mediated structural changes within HSA, along with a comprehensive rationale for the biological transport and accumulation of selonsertib in the blood plasma. Conclusion: Therefore, considering the bioavailability and effectiveness of selonsertib, assessing the interactions of this inhibitor with carrier proteins is crucial to elucidate its biological processes at the molecular level. This evidence carries the considerable scientific potential for future drug design.