Crotonylation at serine 46 impairs p53 activity.

Post-translational modifications (PTMs) play pivotal roles in controlling the stability and activity of the tumor suppressor p53 in response to distinct stressors. Here we report an unexpected finding of a short chain fatty acid modification of p53 in human cells. Crotonic acid (CA) treatment induces p53 crotonylation, but surprisingly reduces its protein, but not mRNA level, leading to inhibition of p53 activity in a dose dependent fashion. Surprisingly this crotonylation targets serine 46, instead of any predicted lysine residues, of p53, as detected in TCEP-probe labeled crotonylation and anti-crotonylated peptide antibody reaction assays. This is further confirmed by substitution of serine 46 with alanine, which abolishes p53 crotonylation in vitro and in cells. CA increases p53-dependent glycolytic activity, and augments cancer cell proliferation in response to metabolic or DNA damage stress. Since serine 46 is only found in human p53, our studies unveil an unconventional PTM unique for human p53, impairing its activity in response to CA. Because CA is likely produced by the gut microbiome, our results also predict that this type of PTM might play a role in early human colorectal neoplasia development by negating p53 activity without mutation of this tumor suppressor gene.

Strategies to target the Hedgehog signaling pathway for cancer therapy.

Hedgehog (Hh) signaling is an essential pathway in the human body, and plays a major role in embryo development and tissue patterning. Constitutive activation of the Hh signaling pathway through sporadic mutations or other mechanisms is explicitly associated with cancer development and progression in various solid malignancies. Therefore, targeted inhibition of the Hh signaling pathway has emerged as an attractive and validated therapeutic strategy for the treatment of a wide range of cancers. Vismodegib, a first-in-class Hh signaling pathway inhibitor was approved by the US Food and Drug Administration in 2012, and sonidegib, another potent Hh pathway inhibitor, received FDA's approval in 2015 as a new treatment of locally advanced or metastatic basal cell carcinoma. The clinical success of vismodegib and sonidegib provided strong support for the development of Hh signaling pathway inhibitors via targeting the smoothened (Smo) receptor. Moreover, Hh signaling pathway inhibitors aimed to target proteins, which are downstream or upstream of Smo, have also been pursued based on the identification of additional therapeutic benefits. Recently, much progress has been made in Hh singling and inhibitors of this pathway. Herein, medicinal chemistry strategies, especially the structural optimization process of different classes of Hh inhibitors, are comprehensively summarized. Further therapeutic potentials and challenges are also discussed.

Quantum Dots-Based Protocols for the Detection of RNAs.

RNA (ribonucleic acid) plays a crucial role in various cellular processes and is involved in the development and progression of several diseases. RNA molecules have gained considerable attention as potential biomarkers for various ailments, as they reflect the activity of genes in a particular cell or tissue. By measuring the levels of specific RNA molecules, such as messenger RNA (mRNA), noncoding RNAs, including microRNAs (miRNAs), and long noncoding RNAs (lncRNAs), researchers can infer the expression patterns of genes associated with a particular disease. Aberrant expression of specific miRNAs or lncRNAs has been associated with conditions such as cancer, cardiovascular diseases, neurodegenerative disorders, and more. Detection and quantification of these RNAs in biological samples, such as blood or tissue, can provide valuable diagnostic or prognostic information. Yet their analysis is a challenging endeavor due to their length, sequence similarity across family members, sensitivity to disintegration, and low quantity in total samples. New advances in nanophotonics have provided novel options for fabrication of quantum dots (QDs)-based biosensing devices capable of detecting a variety of disease-specific RNAs. Thus, we proposed and designed a nanophotonic method employing oligonucleotide-conjugated quantum dot nanoconjugates for the rapid and accurate detection of RNAs. Despite the abundance of other molecules in the sample, the approach delivers highly selective, precise identification of the target RNAs. The data also indicated the method's great practicality and simplicity in determining RNAs selectively. Overall, the approach enables the evaluation of RNA expression in relation to the initial onset and progression of a human health disorder.

Phytometabolites as modulators of breast cancer: a comprehensive review of mechanistic insights.

Breast cancer (BC) is a highly debilitating malignancy affecting females globally and imposing a substantial burden on healthcare systems in both developed and developing nations. Despite the application of conventional therapeutic modalities such as chemotherapy, radiation therapy, and hormonal intervention, BC frequently exhibits resistance, necessitating the urgent development of novel, cost-effective, and accessible treatment strategies. In this context, there is a growing scientific interest in exploring the pharmacological potential of chemical compounds derived from botanical sources, which often exhibit notable biological activity. Extensive in vitro and in vivo investigations have revealed the capacity of these compounds, referred to as phytochemicals, to attenuate the metastatic cascade and reduce the risk of cancer dissemination. These phytochemicals exert their effects through modulation of key molecular and metabolic processes, including regulation of the cell cycle, induction of apoptotic cell death, inhibition of angiogenesis, and suppression of metastatic progression. To shed light on the latest advancements in this field, a comprehensive review of the scientific literature has been conducted, focusing on secondary metabolite agents that have recently been investigated and have demonstrated promising anticancer properties. This review aims to delineate their underlying mechanisms of action and elucidate the associated signaling pathways, thereby contributing to a deeper understanding of their therapeutic potential in the context of BC management.

Virtual screening and molecular dynamics simulation approach for the identification of potential multi-target directed ligands for the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial neurological disorder characterized by memory loss and cognitive impairment. The currently available single-targeting drugs have miserably failed in the treatment of AD, and multi-target directed ligands (MTDLs) are being explored as an alternative treatment strategy. Cholinesterase and monoamine oxidase enzymes are reported to play a crucial role in the pathology of AD, and multipotent ligands targeting these two enzymes simultaneously are under various phases of design and development. Recent studies have revealed that computational approaches are robust and trusted tools for identifying novel therapeutics. The current research work is focused on the development of potential multi-target directed ligands that simultaneously inhibit acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B) enzymes employing a structure-based virtual screening (SBVS) approach. The ASINEX database was screened after applying pan assay interference and drug-likeness filter to identify novel molecules using three docking precision criteria; High Throughput Virtual Screening (HTVS), Standard Precision (SP), and Extra Precision (XP). Additionally, binding free energy calculations, ADME, and molecular dynamic simulations were employed to get structural insights into the mechanism of protein-ligand binding and pharmacokinetic properties. Three lead molecules viz. AOP19078710, BAS00314308 and BDD26909696 were successfully identified with binding scores of -10.565, -10.543 & -8.066 kcal/mol against AChE and -11.019, -12.357 & -10.068 kcal/mol against MAO-B, better score as compared to the standard inhibitors. In the near future, these molecules will be synthesized and evaluated through in vitro and in vivo assays for their inhibition potential against AChE and MAO-B enzymes.

An amalgamated molecular dynamic and Gaussian based 3D-QSAR study for the design of 2,4-thiazolidinediones as potential PTP1B inhibitors.

Overexpression of protein tyrosine phosphatase 1B (PTP1B) is the major cause of various diseases such as diabetes, obesity, and cancer. PTP1B has been identified as a negative regulator of the insulin signaling cascade, thereby causing diabetes. Numerous anti-diabetic medications based on thiazolidinedione have been successfully developed; however, 2,4-thiazolidinedione (2,4-TZD) scaffolds have been reported as potential PTP1B inhibitors for the manifestation of type 2 diabetes mellitus involving insulin resistance. In the present study, we have employed amalgamated approach involving MD-simulation studies (100 ns) as well as Gaussian field-based 3D-QSAR to develop a pharmacophoric model of 2,4-TZD as potent PTP1B inhibitors. MD simulation studies of the most potent compound in the PTP1B (PDB Id: 2QBS) binding pocket revealed that compound 43 was stable in the binding pocket and demonstrated excellent binding efficacy within the active site pocket. MM/GBSA results revealed that compound 43, bearing C-5 arylidine substitution, strongly bound to the target as compared to rosiglitazone with ΔGMM/GBSA difference of -11.13 kcal/mol. PCA, Rg, RMSF, RMSD, and SASA were analyzed from the complex's trajectories to anticipate the simulation outcome. We have suggested a series of 2,4-TZD as possible PTP1B inhibitors based on the results of MD simulation and 3D-QSAR studies.

Nutrient-epigenome interactions: Implications for personalized nutrition against aging-associated diseases.

Aging is a multifaceted process involving genetic and environmental interactions often resulting in epigenetic changes, potentially leading to aging-related diseases. Various strategies, like dietary interventions and calorie restrictions, have been employed to modify these epigenetic landscapes. A burgeoning field of interest focuses on the role of microbiota in human health, emphasizing system biology and computational approaches. These methods help decipher the intricate interplay between diet and gut microbiota, facilitating the creation of personalized nutrition strategies. In this review, we analysed the mechanisms related to nutritional interventions while highlighting the influence of dietary strategies, like calorie restriction and intermittent fasting, on microbial composition and function. We explore how gut microbiota affects the efficacy of interventions using tools like multi-omics data integration, network analysis, and machine learning. These tools enable us to pinpoint critical regulatory elements and generate individualized models for dietary responses. Lastly, we emphasize the need for a deeper comprehension of nutrient-epigenome interactions and the potential of personalized nutrition informed by individual genetic and epigenetic profiles. As knowledge and technology advance, dietary epigenetics stands on the cusp of reshaping our strategy against aging and related diseases.

A comprehensive review on pharmacognosy, phytochemistry and pharmacological activities of 8 potent species of southeast Asia.

Genus Prunus comprising around 430 species is a vast important genus of family Rosaceae, subfamily amygdalaoidae. Among all 430 species, around 19 important species are commonly found in Indian sub-continent due to their broad nutritional and economic importance. Some most common species of genus Prunus are Prunus amygdalus, Prunus persica, Prunus armeniaca, Prunus avium, Prunus cerasus, Prunus cerasoides, Prunus domestica, Prunus mahaleb, etc. A newly introduced species of Prunus i.e Prunus sunhangii is recently discovered which is morphologically very similar to Prunus cerasoides. Plants of Prunus species are short to medium-sized deciduous trees mainly found in the northern hemisphere. In India and its subcontinent, it extends from the Himalayas to Sikkim, Meghalaya, Bhutan, Myanmar etc. Different Prunus species have been extensively studied for their morphological, microscopic, pharmacological and phytoconstituents characteristics. Total phenolic content of Prunus species explains the presence of phenols in high quantity and pharmacological activity due to phenols. Phytochemical screening of species of genus Prunus shows the presence of wide phytoconstituents which contributes in their pharmacological significance and reveals the therapeutic potential and traditional medicinal significance of this genus. Genus Prunus showed a potent antioxidant activity analyzed by 1,1-diphenyl-2-picryl-hydrazyl radical assay. Plant species belonging to the genus Prunus is widely used traditionally for the treatment of various disorders. Some specific Prunus species possess potent anticancer, anti-inflammatory, hypoglycemic etc. activity which makes the genus more interesting for further research and findings. This review is an attempt to summarize the comprehensive study of Prunus.

Exploring the Potential of Essential Oil from Plectranthus amboinicus Leaves against Breast Cancer: In vitro and In silico Analysis.

Plectranthus amboinicus leaves were subjected to hydrodistillation to obtain essential oil (EO). Phytochemical analysis using gas chromatography-mass spectrometry revealed a diverse range of compounds in the EO, with p-cymen-4-ol (18.57%) emerging as the most predominant, followed by isocaryophyllene (12.18%). The in vitro antiproliferative activity of EO against breast cancer was assessed in MCF-7 and MDA-MB-231 cell lines. The MTT assay results revealed that EO showed IC50 values of 42.25 µg/mL and 13.44 µg/mL in MCF-7 cells and 63.67 µg/mL and 26.58 µg/mL in MDA-MB-231 cells after 24 and 48 h, respectively. The in silico physicochemical and pharmacokinetic profiles of the EO constituents were within acceptable limits. Molecular docking was conducted to investigate the interactions between the constituents of the EO and protein Aromatase (PDB ID:3S79). Among the EO constituents, 4-tert-butyl-2-(5-tert-butyl-2-hydroxyphenyl)phenol (4BHP) exhibited the highest dock score of -6.580 kcal/mol when compared to the reference drug, Letrozole (-5.694 kcal/mol), but was slightly lesser than Anastrozole (-7.08 kcal/mol). Molecular dynamics simulation studies (100 ns) of the 4BHP complex were performed to study its stability patterns. The RMSD and RMSF values of the 4BHP protein complex were found to be 2.03 Å and 4.46 Å, respectively. The binding free energy calculations revealed that 4BHP displayed the highest negative binding energy of -43 kcal/mol with aromatase protein, compared to Anastrozole (-40.59 kcal/mol) and Letrozole (-44.54 kcal/mol). However, further research is required to determine the safety, efficacy, and mechanism of action of the volatile oil. Taking into consideration the key findings of the present work, the development of a formulation of essential oil remains a challenging task and novel drug delivery systems may lead to site-specific and targeted delivery for the effective treatment of breast cancer.

Elacestrant: a new FDA-approved SERD for the treatment of breast cancer.

Elacestrant (RAD-1901), a selective estrogen receptor degrader, was approved by USFDA on January 27, 2023, for the treatment of breast cancer. It has been developed by Menarini Group under the brand name Orserdu®. Elacestrant showed anticancer activity both in vitro and in vivo in ER+ HER2-positive breast cancer models. The present review delebrates the development stages of Elacestrant, with its medicinal chemistry, synthesis, mechanism of action, and pharmacokinetic studies. Clinical data and safety profile has also been discussed, including data from randomized trials.

Selective Estrogen receptor degraders (SERDs) for the treatment of breast cancer: An overview.

Discovery of SERDs has changed the direction of anticancer research, as more than 70% of breast cancer cases are estrogen receptor positive (ER+). Therapies such as selective estrogen receptor modulators (SERM) and aromatase inhibitors (AI's) have been effective, but due to endocrine resistance, SERDs are now considered essential therapeutics for the treatment of ER+ breast cancer. The present review deliberates the pathophysiology of SERDs from the literature covering various molecules in clinical trials. Estrogen receptors active sites distinguishing characteristics and interactions with currently available FDA-approved drugs have also been discussed. Designing strategy of previously reported SERDs, their SAR analysis, in silico, and the biological efficacy have also been summarized along with appropriate examples.

Current Insights into the Role of BRAF Inhibitors in Treatment of Melanoma.

Melanomas represent only 4% of all skin cancers, but their mortality rate is more than 50 % of any other skin cancer. Alteration in genetic and environmental factors are the risk factors for melanoma development. The RAS/RAF/MEK/ERK or Mitogen-activated protein kinase (MAPK) pathway is activated in melanoma. BRAF activation is necessary to govern differentiation, proliferation, and survival. Mutations in BRAF were found in 80-90% of all melanomas. Over 90% of BRAF mutations occur at codon 600, and over 90% of them are BRAFV600E other common mutations are BRAFV600K, BRAFV600R, BRAF V600'E2', and BRAF V600D. Based on αC-helix and DFG motif (αC-helix-IN/DFG-IN), (αC-helix-IN/DFG-OUT), (αC-helix-OUT/DFG-IN) and (αC-helix-OUT/ DFG-OUT) are four structural types of inhibitors for targeting BRAF. Sorafenib, Vemurafenib, Dabrafenib, and Encorafenib are FDAapproved for the treatment of BRAF. Understanding melanoma pathogenesis, RAS/RAF/MEK/ERK or MAPK pathway, and BRAF conformations, mutations, the problems with FDA approved BRAF inhibitors will be important for new drug discovery, modification of existing BRAF barriers to improve target specific action, and prevent increasing response levels while minimizing toxicity.

Molecular dynamics and 3D-QSAR studies on indazole derivatives as HIF-1α inhibitors.

Hypoxia-inducible factor (HIF) is a transcriptional factor which plays a crucial role in tumour metastasis thereby responsible for development of various forms of cancers. Indazole derivatives have been reported in the literature as potent HIF-1α inhibitor via interaction with key residues of the HIF-1α active site. Taking into consideration the role HIF-1α in cancer and potency of indazole derivative against HIF-1α; it was considered of interest to correlate structural features of known indazole derivatives with specified HIF-1α inhibitory activity to map pharmacophoric features through Three-dimensional quantitative structural activity relationship (3D-QSAR) and pharmacophore mapping. Field and Gaussian based 3D-QSAR studies were performed to realize the variables influencing the inhibitory potency of HIF-1α inhibitors. Field and Gaussian- based 3D-QSAR models were validated through various statistical measures generated by partial least square (PLS). The steric and electrostatic maps generated for both 3D-QSAR provide a structural framework for designing new inhibitors. Further; 3D-maps were also helpful in understanding variability in the activity of the compounds. Pharmacophore mapping also generates a common five-point pharmacophore hypothesis (A1D2R3R4R5_4) which can be employed in combination with 3D-contour maps to design potent HIF-1α inhibitors. Molecular docking and molecular dynamics (MD) simulation of the most potent compound 39 showed good binding efficiency and was found to be quite stable in the active site of the HIF-1α protein. The developed 3D-QSAR models; pharmacophore modelling; molecular docking studies along with the MD simulation analysis may be employed to design lead molecule as selective HIF-1α inhibitors for the treatment of Cancer.

Molecular docking, 3D-QSAR and simulation studies for identifying pharmacophoric features of indole derivatives as 17ß-hydroxysteroid dehydrogenase type 5 (17ß-HSD5) inhibitors.

Excess of androgens leads to various diseases such as Poly-Cystic Ovarian Syndrome, Prostate Cancer, Hirsutism, Obesity and Acne. 17ß-Hydroxysteroid Dehydrogenase type 5 (17ß-HSD5) converts androstenedione into testosterone peripherally, thereby significantly contributing to the development of these diseases. Indole-bearing scaffolds are reported as potential 17ß-HSD5 inhibitors for the manifestation of diseases arising due to androgen excess. In the present work, we have extensively performed a combination of molecular docking, Gaussian field-based 3D-QSAR, Pharmacophore mapping and MD-simulation studies (100 ns) to identify the pharmacophoric features of indole-based compounds as potent 17ß-HSD5 inhibitors. Molecular simulation studies of the most potent compound in the binding pocket of enzyme revealed that the compound 11 was stable in the binding pocket and showed good binding affinity through interactions with various residues of active site pocket. The Molecular mechanics Generalized Born surface area continuum solvation (MM/GBSA) and Molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations revealed that the compound 11 possessed a free binding energy of -36.36 kcal/mol and -7.00 kcal/mol, respectively, which was better as compared to reference compound Desmethyl indomethacin (DES). The developed pharmacophore will be helpful to design novel indole-based molecules as potent 17ß-HSD5 inhibitors for the treatment of various androgenic disorders.Communicated by Ramaswamy H. Sarma.

Current development of 1,2,3-triazole derived potential antimalarial scaffolds: Structure- activity relationship (SAR) and bioactive compounds.

Malaria is among one of the most devastating and deadliest parasitic disease in the world claiming millions of lives every year around the globe. It is a mosquito-borne infectious disease caused by various species of the parasitic protozoan of the genus Plasmodium. The indiscriminate exploitation of the clinically used antimalarial drugs led to the development of various drug-resistant and multidrug-resistant strains of plasmodium which severely reduces the therapeutic effectiveness of most frontline medicines. Therefore, there is urgent need to develop novel structural classes of antimalarial agents acting with unique mechanism of action(s). In this context, design and development of hybrid molecules containing pharmacophoric features of different lead molecules in a single entity represents a unique strategy for the development of next-generation antimalarial drugs. Research efforts by the scientific community over the past few years has led to the identification and development of several heterocyclic small molecules as antimalarial agents with high potency, less toxicity and desired efficacy. Triazole derivatives have become indispensable units in the medicinal chemistry due to their diverse spectrum of biological profiles and many triazole based hybrids and conjugates have demonstrated potential in vitro and in vivo antimalarial activities. The manuscript compiled recent developments in the medicinal chemistry of triazole based small heterocyclic molecules as antimalarial agents and discusses various reported biologically active compounds to lay the groundwork for the rationale design and discovery of triazole based antimalarial compounds. The article emphasised on biological activities, structure activity relationships, and molecular docking studies of various triazole based hybrids with heterocycles such as quinoline, artemisinins, naphthyl, naphthoquinone, etc. as potential antimalarial agents which could act on the dual stage and multi stage of the parasitic life cycle.

Dual aromatase-steroid sulfatase inhibitors (DASI's) for the treatment of breast cancer: a structure guided ligand based designing approach.

Dual aromatase-steroid sulfatase inhibitors (DASIs) lead to significant deprivation of estrogen levels as compared to a single target inhibition and thereby exhibited an additive or synergistic effect in the treatment of hormone-dependent breast cancer (HDBC). Triazole-bearing DASI's having structural features of clinically available aromatase inhibitors are identified as lead structures for optimization as DASI's. To identify the spatial fingerprints of target-specific triazole as DASI's, we have performed molecular docking assisted Gaussian field-based comparative 3D-QSAR studies on a dataset with dual aromatase-STS inhibitory activities. Separate contours were generated for both aromatase and steroid sulphates showing respective pharmacophoric structural requirements for optimal activity. These developed 3D-QSAR models also showed good statistical measures with the excellent predictive ability with PLS-generated validation constraints. Comparative steric, electrostatic, hydrophobic, HBA, and HBD features were elucidated using respective contour maps for selective target-specific favourable activity. Furthermore, the molecular docking was used for elucidating the mode of binding as DASI's along with the MD simulation of 100 ns revealed that all the protease-ligand docked complexes are overall stable as compared to reference ligand (inhibitor ASD or Irosustat) complex. Further, the MM-GBSA study revealed that compound 24 binds to aromatase as well as STS active site with relatively lower binding energy than reference complex, respectively. A comparative study of these developed multitargeted QSAR models along with molecular docking and dynamics study can be employed for the optimization of drug candidates as DASI's.Communicated by Ramaswamy H. Sarma.

Pharmacophore derived 3D-QSAR, molecular docking, and simulation studies of quinoxaline derivatives as ALR2 inhibitors.

Aldose Reductase 2 (ALR2), a key enzyme of the polyol pathway, plays a crucial role in the pathogenesis of diabetic complications. Quinoxaline scaffold-based compounds have been identified as potential ALR2 inhibitors for the management of diabetic complications. In the present work, molecular dynamic simulation studies in conjugation with pharmacophore mapping and atom-based 3D-QSAR were performed on a dataset of 99 molecules in comparison with Epalrestat (reference) to mark the desirable structural features of quinoxaline analogs to generate a probable template for designing novel and effective ALR2 inhibitors. The most potent compound 81 was subjected to MD simulation studies and found to be stable, with better interactions with the binding pocket as compared to Epalrestat. The MM-GBSA and MM-PBSA calculations showed that compound 81 possessed binding free energies of -35.96 and -4.92 kcal/mol, respectively. Atom-based 3D-QSAR yielded various pharmacophoric features with excellent statistical measures, such as correlation coefficient (R2 value), F-value (Fischer ratio), Q2 value (cross-validated correlation coefficient), and Pearson's R-value for training and test sets. Furthermore, the pharmacophore mapping provided a five-point hypothesis (AADRR) and docking analysis revealed the active ligand-binding orientations on the active site's amino acid residues TYR 48, HIE 110, TRP 111, and TRP 219. The results of this study will help in designing potent inhibitors of ALR2 for the management of diabetic complications.Communicated by Ramaswamy H. Sarma.

Recent Advancements in the Discovery of MDM2/MDM2-p53 Interaction Inhibitors for the Treatment of Cancer.

Discovery of MDM2 and MDM2-p53 interaction inhibitors changed the direction of anticancer research as it is involved in about 50% of cancer cases globally. Not only the inhibition of MDM2 but also its interaction with p53 proved to be an effective strategy in anticancer drug design and development. Various molecules of natural as well as synthetic origin have been reported to possess excellent MDM2 inhibitory potential. The present review discusses the pathophysiology of the MDM2-p53 interaction loop and MDM2/MDM2-p53 interaction inhibitors from literature covering recent patents. Focus has also been put on characteristic features of the active site of the target and its desired interactions with the currently FDA-approved inhibitor. The designing approach of previously reported MDM2/MDM2-p53 interaction inhibitors, their SAR studies, in silico studies, and the biological efficacy of various inhibitors from natural as well as synthetic origins are also elaborated. An attempt is made to cover recently patented MDM2/MDM2- p53 interaction inhibitors.

Microsponges as Drug Delivery System: Past, Present, and Future Perspectives.

Microsponges are polymeric delivery devices composed of porous microspheres that range in size from 5 to 300 micrometers. These have been explored for biomedical applications such as targeted drug delivery, transdermal drug delivery, anticancer drug delivery, and bone substitutes. The purpose of this study is to conduct a comprehensive analysis of recent developments and prospects for a microsponge-based drug delivery system. The current study analyzes how the Microsponge Delivery System (MDS) is made, how it works, and how it can be used for a wide range of therapeutic purposes. The therapeutic potential and patent information of microsponge-based formulations were systematically analyzed. The authors summarize various effective techniques for developing microsponges, such as liquid-liquid suspension polymerization, quasi-emulsion solvent diffusion method, water-in-oil-in-water (w/o/w) emulsion solvent diffusion, oil-in-oil emulsion solvent diffusion, lyophilization method, porogen addition method, vibrating orifice aerosol generator method, electrohydrodynamic atomization method, and ultrasound-assisted microsponge. Microsponge may reduce the side effects and increase drug stability by positively altering drug release. Drugs that are both hydrophilic and hydrophobic can be loaded into a microsponge and delivered to a specific target. The microsponge delivery technology offers numerous advantages over conventional delivery systems. Microsponges, which are spherical sponge-like nanoparticles with porous surfaces, have the potential to increase the stability of medications. They also efficiently decrease the undesirable effects and alter drug release.

Boron in cancer therapeutics: An overview.

Boron has become a crucial weapon in anticancer research due to its significant intervention in cell proliferation. Being an excellent bio-isosteric replacement of carbon, it has modulated the anticancer efficacy of various molecules in the development pipeline. It has elicited promising results through interactions with various therapeutic targets such as HIF-1α, steroid sulfatase, arginase, proteasome, etc. Since boron liberates alpha particles, it has a wide-scale application in Boron Neutron Capture therapy (BNCT), a radiotherapy that demonstrates selectivity towards cancer cells due to high boron uptake capacity. Significant advances in the medicinal chemistry of boronated compounds, such as boronated sugars, natural/unnatural amino acids, boronated DNA binders, etc., have been reported over the past few years as BNCT agents. In addition, boronated nanoparticles have assisted the field of bio-nano medicines by their usage in radiotherapy. This review exclusively focuses on the medicinal chemistry aspects, radiotherapeutic, and chemotherapeutic aspects of boron in cancer therapeutics. Emphasis is also given on the mechanism of action along with advantages over conventional therapies.