Globally, one of the most prevalent cancers is colorectal cancer (CRC). Chemotherapy and surgery are two common conventional CRC therapies that are frequently ineffective and have serious adverse effects. Thus, there is a need for complementary and different therapeutic approaches. The use of microbial metabolites to trigger epigenetic alterations as a way of preventing CRC is one newly emerging field of inquiry. Small chemicals called microbial metabolites, which are made by microbes and capable of altering host cell behaviour, are created. Recent research has demonstrated that these metabolites can lead to epigenetic modifications such as histone modifications, DNA methylation, and non-coding RNA regulation, which can control gene expression and affect cellular behaviour. This review highlights the current knowledge on the epigenetic modification for cancer treatment, immunomodulatory and anti-carcinogenic attributes of microbial metabolites, gut epigenetic targeting system, and the role of dietary fibre and gut microbiota in cancer treatment. It also focuses on short-chain fatty acids, especially butyrates (which are generated by microbes), and their cancer treatment perspective, challenges, and limitations, as well as state-of-the-art research on microbial metabolites-induced epigenetic changes for CRC inhibition. In conclusion, the present work highlights the potential of microbial metabolites-induced epigenetic modifications as a novel therapeutic strategy for CRC suppression and guides future research directions in this dynamic field.
Fused heterocyclic imidazonaphthyridine compounds stand at the forefront of global research, captivating remarkable interest in medicinal and synthetic organic chemistry. These compounds possess a range of potent biological and pharmacological properties, rendering them invaluable for medical and therapeutic research, particularly in drug design and discovery. Despite their significance, no dedicated review has focused on fused heterocyclic imidazonaphthyridine derivatives. This comprehensive review aims to consolidate and explore the cutting-edge synthesis approaches tailored specifically for these unique imidazonaphthyridine derivatives. It highlights their current applications in various biological realms and provides insights into potential future trajectories. By steering forthcoming research endeavours towards innovative design and synthesis of novel imidazonaphthyridines, this review seeks to diversify these compounds, paving the way for biological applications that have yet to be fully realized. Overall, as a burgeoning area of research, this review underscores the potential of imidazonaphthyridines as promising candidates for biomedical applications, offering a snapshot of current research and suggesting future avenues for investigation.
Eleven undescribed triterpenoids (pentandrucines A to K) were isolated from the n-hexane extract of the stem bark of Chisocheton pentandrus (Blanco) Merr. These comprised ten undescribed dammarane-type triterpenoids and one undescribed apotirucallane-type triterpenoid. Additionally, two dammarane-type triterpenoids, four apotirucallane-type triterpenoids and two tirucallane-type triterpenoids were also isolated. The chemical structures of pentandrucine A-K, were fully elucidated using 1D and 2D-NMR, and high resolution MS. All of the compounds were evaluated for cytotoxic activity against MCF-7 breast cancer cells in vitro. Melianodiol proved to be the most active with an IC50 of 16.84 μM comparing favourably with Cisplatin (13.2 μM).
Recently, studies on the development and investigation of carbohydrate-functionalized silica nanoparticles (NPs) and their biomedicine applications such as cell-specific targeting and bioimaging has been carried out extensively. Since the number of breast cancer patients has been growing in recent years, potential NPs were being studied in this project for targeting breast cancer cells. Mannose receptors can be found on the surface of MDA-MB-231, which is a kind of human breast cancer cell line. Therefore, we decorated a cyanine 3 fluorescent dye (Cy3) and mannosides on the surface of silica NPs for the purpose of imaging and targeting. Galactoside was also introduced onto the surface of silica NPs acting as a control sample. Various sizes of silica NPs were synthesized by using different amounts of ammonium to investigate the effect of the size of NPs on the cellular uptake rate. The physical properties of these NPs were characterized by scanning electron microscope, dynamic light scattering, and their zeta potential. Cellular experiments demonstrated that mannoside-modified NPs can be uptaken by MDA-MB-231. From the experiment, we found out that the best cellular uptake rate of nanoparticle size is about 250 nm. The MTT assay showed that Man@Cy3SiO2NPs are not cytotoxic, indicating they may have the potential for biomedical applications.
A seco-apotirucallane-type triterpenoid, namely angustifolianin (1), along with three dammarane-type triterpenoids, (20S, 24S)-epoxy-dammarane-3β,25-diol (2), 3-epi-cabraleahydroxylactone (3), and cabralealactone (4), were isolated from the stem bark of Aglaia angustifolia Miq. The Chemical structure of the new compounds was elucidated on the basis of spectroscopic data. All of the compounds were evaluated for their cytotoxic effects against MCF-7 breast cancer cells. Among those compounds, angustifolianin (1) showed strongest cytotoxic activity with an IC50 value of 50.5 μg/ml.
A new era of metal-based drugs started in the 1960s, heralded by the discovery of potent platinum-based complexes, commencing with cisplatin [(H₃N)₂PtCl₂], which are effective anti-cancer chemotherapeutic drugs. While clinical applications of gold-based drugs largely relate to the treatment of rheumatoid arthritis, attention has turned to the investigation of the efficacy of gold(I) and gold(III) compounds for anti-cancer applications. This review article provides an account of the latest research conducted during the last decade or so on the development of gold compounds and their potential activities against several cancers as well as a summary of possible mechanisms of action/biological targets. The promising activities and increasing knowledge of gold-based drug metabolism ensures that continued efforts will be made to develop gold-based anti-cancer agents.
Colorectal cancer (CRC) remains a leading cause of death globally despite the improvements in cancer treatment. Autophagy is an evolutionarily conserved lysosomal-dependent degradation pathway that is critical in maintaining cellular homeostasis. However, in cancer, autophagy may have conflicting functions in preventing early tumour formation versus the maintenance of advanced-stage tumours. Defective autophagy has a broad and dynamic effect not just on cancer cells, but also on the tumour microenvironment which influences tumour progression and response to treatment. To add to the layer of complexity, somatic mutations in CRC including tumour protein p53 (TP53), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), Kirsten rat sarcoma viral oncogene homolog (KRAS), and phosphatase and tensin homolog (PTEN) can render chemoresistance by promoting a pro-survival advantage through autophagy. Recent studies have also reported autophagy-related cell deaths that are distinct from classical autophagy by employing parts of the autophagic machinery, which impacts strategies for autophagy regulation in cancer therapy. This review discusses the molecular processes of autophagy in the evolution of CRC and its role in the tumour microenvironment, as well as prospective therapeutic methods based on autophagy suppression or promotion. It also highlights clinical trials using autophagy modulators for treating CRC, underscoring the importance of autophagy regulation in CRC therapy.
Matched MeSH terms: Antineoplastic Agents/pharmacology; Antineoplastic Agents/therapeutic use
Lung malignancies are among the most prevalent and foremost causes of tumor-related deaths. Despite significant advancements in the understanding and management of lung cancer, resistance to traditional treatments remains a significant challenge. Understanding and targeting tumor microenvironment (TME) have attracted interest in the recent decade for eliminating various solid tumors. The lung TME has a crucial position in tumor expansion and therapy failure, driving it an engaging target for novel medicinal interventions. Plant-derived products offer a promising avenue for targeting TME due to their diverse chemical structures and biological activities. However, their clinical use is hindered by insufficient bioavailability and also possible systemic toxicity. The use of nanoparticles as delivery vehicles for natural products can overcome these challenges and enhance their therapeutic efficacy. This review article explores the potential of plant-derived products as medicinal agents for targeting lung TME. We provide an outline of the present knowledge of lung TME and explain the mechanisms by which plant-derived products can modulate key components of this microenvironment. The promising impacts and properties of nanoparticles for the delivery of these derivatives into lung tumors will also be discussed. We also review the preclinical and clinical findings for supporting the usefulness of these agents in targeting lung TME. Additionally, we highlight the challenges and forthcoming trends in the development of plant-derived products as targeted therapies for lung cancer, with a particular focus on combination therapies.
Matched MeSH terms: Antineoplastic Agents, Phytogenic/pharmacology; Antineoplastic Agents, Phytogenic/therapeutic use
Mushrooms are considered one of the safe and effective medications because they have great economic importance due to countless biological properties. Cordyceps militaris contains bioactive compounds with antioxidant, antimicrobial and anti-cancerous properties. This study was projected to analyze the potentials of biometabolites and to extract antimicrobial peptides and protein from the C. militaris. An in-vitro analysis of biometabolites and antimicrobial peptides was performed to investigate their pharmacological potentials followed by quantification and characterization of extracted protein. Computational analysis on non-small cell lung cancer genes (NSCLC) was performed on quantified compounds to interpret the biometabolites from C. militaris that could be potential drug candidate molecules with high specificity and potency. A total of 34 compounds representing 100% of total detected constituents identified were identified using GCMS analysis and 20 compounds using LC-MS which showed strong biological activities. FT-IR spectroscopy manifest powerful instant peaks to have different bioactive components including carboxylic acid, phenols, amines and alkanes present in methanolic extract of C. militaris. In C. militaris, higher protein concentration was observed in 70% concentration of protein extract (500 μg/ml ± 0.025). The best antioxidant activity (% Radical scavenging activity) of methanolic extracts was 80a ± 0.03, antidiabetic activity was 37 ± 0.057 and anti-inflammatory activity was 40 ± 0.021 at 12 mg/ml. Antibacterial activity for different concentrations of Cordyceps protein and methanolic extracts was significantly (p < 0.05). Indolizine, 2-(4-methylphenyl) has most binding affinity (micromolar) and optimized properties to be selected as the lead inhibitor. It interacts favorably with the active site of RET gene of NSCLC and is neuroprotective and hepatoprotective.
Almost 70% of clinically used antineoplastic drugs are originated from natural products such as plants, marine organism, and microorganisms and some of them are also structurally modified natural products. The naturally occurring drugs may specifically act as inducers of selective cytotoxicity, anti-metastatic, anti-mutagenic, anti-angiogenesis, antioxidant accelerators, apoptosis inducers, autophagy inducers, and cell cycle inhibitors in cancer therapy. Precisely, several reports have demonstrated the involvement of naturally occurring anti-breast cancer drugs in regulating the expression of oncogenic and tumor suppressors associated with carcinogen metabolism and signaling pathways. Anticancer therapies based on nanotechnology have the potential to improve patient outcomes through targeted therapy, improved drug delivery, and combination therapies. This paper has reviewed the current treatment for breast cancer and the potential disadvantages of those therapies, besides the various mechanism used by naturally occurring phytochemicals to induce apoptosis in different types of breast cancer. Along with this, the contribution of nanotechnology in improving the effectiveness of anticancer drugs was also reviewed. With the development of sciences and technologies, phytochemicals derived from natural products are continuously discovered; however, the search for novel natural products as chemoprevention drugs is still ongoing, especially for the advanced stage of breast cancer. Continued research and development in this field hold great promise for advancing cancer care and improving patient outcomes.
The conversion of lignin into bioactive compounds through selective organic synthesis methods represents a promising frontier in the pursuit of sustainable raw materials and green chemistry. This review explores the versatility of lignin-derived bioactive compounds, ranging from their application in drug discovery to their role in the development of biodegradable materials. Despite notable advancements, the synthesis routes and yields of highly bioactive molecules from lignin still require further exploration and improvement. This review provides an in-depth examination of the progress made in understanding the complex structure of lignin and developing innovative approaches to exploit its potential. Specifically, the types of lignins covered include softwood Kraft lignin, hardwood organosolv lignin, and soda lignin. This work is divided into three parts: first, the transformation of lignin into bioactive molecules with chemically active centres and functionalised hydroxyl groups through depolymerisation; second, kinetic modelling techniques essential for understanding the chemical kinetics of lignin and enabling significant scaling up in the conversion of organic molecules; third, efficient catalytic pathways for synthesising molecules with anticancer and antibacterial properties. In conclusion, this comprehensive review spurs further investigations into lignin-derived bioactive compounds, their applications, and the advancement of sustainable processes.
Cancer continues to pose a formidable threat, claiming millions of lives annually. A beacon of hope in this battle lies in the realm of bioactive glasses, which have undergone a remarkable evolution over the past five decades. Among these, mesoporous bioactive glasses (MBGs) emerge as a dynamic subset endowed with customizable attributes such as high surface area and porosity. While holding immense promise for cancer care, the full clinical potential of MBGs remains largely unexplored. This review delves into the cutting-edge advancements in MBG technology, illuminating their pivotal role in cancer management - spanning from early detection to targeted therapeutic interventions like photothermal and photodynamic treatments. Furthermore, the molecular mechanisms underpinning MBGs' anticancer properties are elucidated, alongside an exploration of existing limitations in their application. Through this comprehensive synthesis, the significance of MBGs in revolutionizing cancer therapy is underscored, underscoring the urgent need for continued research to unlock their full potential in reshaping the landscape of cancer care.
Two new azadirone-type limonoids, namely lasiocarpine A (1) and lasiocarpine B (2) were isolated from the fruit of Chisocheton lasiocarpus along with three known limonoids (3-5). UV, IR, one- and two- dimensional NMR, and mass spectrometry were used to determine the chemical structure of the isolated compounds. Furthermore, their cytotoxic activity against breast cancer cell line MCF-7 was evaluated using PrestoBlue reagent. From these compounds, lasiocarpine A (1) showed the strongest activity with an IC50 value of 43.38 μM.
Lung cancer is the most common type of cancer, with over 2.1 million cases diagnosed annually worldwide. It has a high incidence and mortality rate, leading to extensive research into various treatment options, including the use of nanomaterial-based carriers for drug delivery. With regard to cancer treatment, the distinct biological and physico-chemical features of nano-structures have acquired considerable impetus as drug delivery system (DDS) for delivering medication combinations or combining diagnostics and targeted therapy. This review focuses on the use of nanomedicine-based drug delivery systems in the treatment of lung cancer, including the use of lipid, polymer, and carbon-based nanomaterials for traditional therapies such as chemotherapy, radiotherapy, and phototherapy. The review also discusses the potential of stimuli-responsive nanomaterials for drug delivery in lung cancer, and the limitations and opportunities for improving the design of nano-based materials for the treatment of non-small cell lung cancer (NSCLC).
Genus Calophyllum is well-known for its phenolic constituents, especially coumarins, which have shown to have a wide range of significant biological activities. In this study, four known phenolic constituents and two triterpenoids have been isolated from the stem bark of Calophyllum lanigerum. The compounds were two pyranochromanone acids are known as caloteysmannic acid (1), isocalolongic acid (2), a simple dihydroxyxanthone, namely euxanthone (3), one coumarin named calanone (4), and two common triterpenoids, friedelin (5), and stigmasterol (6). Chromanone acids were reported for the first time in this Calophyllum species. Cytotoxic evaluations were carried out on n-hexane extract (87.14 ± 2.04 µg/mL; 81.46 ± 2.42 µg/mL) followed by the chromanone acids (1 [79.96 ± 2.39 µM; 83.41 ± 3.39 µM] & 2 [57.88 ± 2.34; 53.04 ± 3.18 µM]) against two cancerous cell lines, MDA-MB-231 and MG-63 cell lines, respectively. The results showed that all tested samples exhibited moderate cytotoxicity.
This study reports the antioxidant potential and L-asparaginase production of culturable fungal endophytes from Dendrobium orchids in Malaysia. Twenty-nine isolates were screened using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay to determine their free radical scavenging activities and antioxidant capacity (IC50 and AEAC). L-asparaginase production of fungal endophytes was detected by the qualitative plate assay, and the enzyme activities estimated via the Nesslerization method. All 29 endophytic isolates exhibited various degrees of radical scavenging activities (35.37%-77.23%), with Fusarium fujikuroi (D1) identified as having the highest antioxidant capacity (IC50 6.097 mg/mL) and the highest AEAC value (11.55 mg/g). For L-asparaginase production, the majority of the isolates (89.66%) showed positive results, especially among the culturable species of Fusarium, Trichoderma, and Daldinia. Most Fusarium spp. were able to produce L-asparaginase (80.77%), but the highest L-asparaginase activity was detected in Daldinia eschscholtzii (D14) with 2.128 units/mL. Results from this study highlighted the potential of endophytic fungi from medicinal orchids (Dendrobium sp.) as natural sources of bioactive compounds to be developed into novel antioxidants and anticancer drugs.
Cancer is the main cause of death worldwide, so the discovery of new and effective therapeutic agents must be urgently addressed. Diatoms are rich in minerals and secondary metabolites such as saturated and unsaturated fatty acids, esters, acyl lipids, sterols, proteins, and flavonoids. These bioactive compounds have been reported as potent anti-cancer, anti-oxidant and anti-bacterial agents. Diatoms are unicellular photosynthetic organisms, which are important in the biogeochemical circulation of silica, nitrogen, and carbon, attributable to their short growth-cycle and high yield. The biosilica of diatoms is potentially effective as a carrier for targeted drug delivery in cancer therapy due to its high surface area, nano-porosity, bio-compatibility, and bio-degradability. In vivo studies have shown no significant symptoms of tissue damage in animal models, suggesting the suitability of a diatoms-based system as a safe nanocarrier in nano-medicine applications. This review presents an overview of diatoms' microalgae possessing anti-cancer activities and the potential role of the diatoms and biosilica in the delivery of anticancer drugs. Diatoms-based antibodies and vitamin B12 as drug carriers are also elaborated.
In order to develop supercritical fluid (SCF) processes for the micro or nanosizing of solid solute components, such as pharmaceuticals, it is essential to assess their solubility in solvents including supercritical carbon dioxide (SC-CO2). This crucial step is fundamental for choosing and evaluating the processes in SCF technology. A statistical method was developed and used to determine the solubility of gemcitabine in SC-CO2. The solubility measurements at various pressures and temperatures were conducted using UV-vis analysis. Two model types were used to correlate the data: semi-empirical (with 3-6 parameters) and equation of state (EoS) models. The solubility of gemcitabine in SC-CO2 using a static method at temperatures of 308-338 K and pressures of 120-270 bar were measured and modeled for the first time. Solubility of gemcitabine ranged from 0.1274 × 10- 5 to 1.8128 × 10- 5 in mole fraction and 0.00295 to 0.08489 kg/L. The PR EoS model performed best at 308 K with an AARD of 12.58%, and SRK excelled at 318-338 K with AARDs between 12.93 and 15.68%. Application of the Joback method (AARD 12.04-27.13%) and COSMO-RS method (AARD 18.68-31.28%) in EoS models also were compared. The Bian et al. model showed the best fit among density-based models with an AARD of 16.62%.