Anticancer Medicines Research Articles

US Trends In Anticancer Medicine Pricing And The Impact Of Competition, 2014-20.

Prices of anticancer medicines (including chemically synthesized medicines and biologics manufactured from living organisms) are a subject of concern, as they contribute to spending by health plans and patients. We describe prices and evaluate the impact of competition among 185 anticancer medicines, using IQVIA data from the period October2014-February2020. We calculated the price of each medicine, defined as volume-weighted wholesale costs net of prompt-pay discounts and gross of rebates, without and with inflation adjustment, and summarized them by patent status, formulation, and therapeutic class. We evaluated the relationship between prices and competition, using regression analyses. We also conducted event studies of the impact of generic entry on the prices of three medicines from distinct clinically relevant therapeutic classes. Over the course of the study period, medicine prices increased among brand-name products and decreased among generics and biosimilars. After exclusivity loss, generic and biosimilar medicine prices decreased, whereas brand-name prices remained stable. Event study results present more divergent price trends after exclusivity loss. Consistent with previous research, our study showed that competition may improve the affordability of medicines for payers and patients. However, this effect is limited for anticancer medicines because only a minority are available as generics and biosimilars.

Do Anticancer Medicinal Compounds have DNMT1 Regulating Activity: An In silico Investigation

Background: DNA methyltransferases (DNMTs) are a group of epigenetic enzymes implicated in regulating gene expression in actively dividing cells. Among these enzymes, DNMT1 plays a leading role in causing increased DNA methylation of tumor suppressors and other genes in cancer cells. This methylation event disrupts the cell cycle regulating genes, allowing an uninterrupted proliferation of cancer cells, and stimulating the inhibition of the degradation of proteins and aberrant transcription activation. Cytosine analog drugs have been shown to reduce DNA methylation but provoke the expression of other prometastatic genes. On the other hand, medicinal compounds act similarly to cytosine analogs by reducing the expression and activity of DNMT1, as reported in some in vitro cancer studies. However, it remains a mystery what those promising medicinal compounds are that show such activity. Objectives: The objective of this study was to screen medicinal compounds that reduce the expression and interact with the active site residues of DNMT1. Methods: To analyze medicinal compounds against DNMT1, two in silico tools were employed: DIGEP-pred and IGEMDOCK to discover and identify 98 lead medicinal compounds having anticancer potential, capable of regulating DNMT1 expression and activity. Results: Our results have identified twenty (20) medicinal compounds that reduced the expression of DNMT1 up to 50-77% as compared to the standard cytosine analog (91.5%). These compounds have also interacted with the reported active site residues of DNMT1, as predicted by IGEMDOCK. These compounds have adequate druglikeness, toxicity, and pharmacokinetic properties as described by Protox-II and ADMET lab 2.0. Conclusion: Thus, our study provides an initial report of those medicinal compounds that have DNMT1 targeting ability and have a relatively safer pharmacokinetic and toxicity profile.

Discovery of novel azo pyrimidinone derivatives as B-cell lymphoma-2 inhibitors with potential antineoplastic activity: Synthesis, characterization, in-silico, and in-vitro studies

In the present investigation, novel azo compounds containing pyrimidinone moiety incorporated with different heterocycles were synthesized and characterized using spectroscopic techniques including FT-IR, 1H-NMR, 13C-NMR, and elemental analysis. These azo derivatives were assessed in- silico to determine how well they could inhibit the antiapoptotic B-cell lymphoma-2 (Bcl-2) protein while providing information about their pharmacokinetic characteristics. Our results elucidated that the majority of these new compounds demonstrated moderate to strong binding energies against Bcl-2 target protein comparable to that of venetoclax FDA-approved Bcl-2 inhibitor. Compound 4 showed the top-ranked binding energy followed by compound 5 and compound 3 with values equal to -11.65, -9.53, and -7.82 kcal/mol respectively, while compounds 6 and 7 showed moderate binding energies compared with venetoclax drug that give binding energy equal to -6.95 kcal/mol Furthermore, the in-vitro investigations observed that compounds 4, 5 and 3 demonstrated superior anticancer efficacy against HepG2 and MCF-7 compared to venetoclax drug that gives IC50 equal to 5.10±0.54 and 4.17±0.8 μM respectively. Moreover, all newly synthesized compounds had no cytotoxic impact on WI-38 normal cells contrary to venetoclax drug (26.72±0.94 μM) which was confirmed also through ADMES drug-likeness scores study. Additionally, compounds 4, 5, and 3 revealed an efficient antioxidant scavenging capacity towards DPPH free radicals while compounds 6 and 7 showed a weak scavenging effect compared with standard L. ascorbic acid. Ultimately, the newly synthesized pyrimidinone compounds 4, 5, and 3 that were examined showed encouraging apoptotic and antiproliferative properties. Further, in upcoming clinical studies, the newly synthesized pyrimidinone compounds may prove to be effective anticancer medicines.

Preparation and Evaluation of pH-Sensitive Chitosan/Alginate Nanohybrid Mucoadhesive Hydrogel Beads: An Effective Approach to a Gastro-Retentive Drug Delivery System.

Despite extensive research over the decades, cancer therapy is still a great challenge because of the non-specific delivery of chemotherapeutic agents, which could be overcome by limiting the distribution of chemotherapeutic agents toward cancer cells. To reduce the cytolytic effects against cancer cells, graphene oxide (GO) nanoparticles (NPs) can load anticancer medicines and genetic tools. During the current study, folic-acid-conjugated graphene oxide (Fa-GO) hybrid mucoadhesive chitosan (CS)-based hydrogel beads were fabricated through an "ion-gelation process", which allows for regulated medication release at malignant pH. The fabricated chitosan-alginate (SA-CS) hydrogel beads were examined using surface morphology, optical microscopy, XRD, FTIR, and homogeneity analysis techniques. The size analysis indicated that the size of the Fa-GO was up to 554.2 ± 95.14 nm, whereas the beads were of a micrometer size. The folic acid conjugation was confirmed by NMR. The results showed that the craggy edges of the graphene oxide were successfully encapsulated in a polymeric matrix. The mucoadhesive properties were enhanced with the increase in the CS concentration. The nanohybrid SA-CS beads exhibited good swelling properties, and the drug release was 68.29% at pH 5.6 during a 24 h investigation. The accelerated stability study, according to ICH guidelines, indicated that the hydrogel beads have a shelf-life of more than two years. Based on the achieved results, it can be concluded that this novel gastro-retentive delivery system may be a viable and different way to improve the stomach retention of anticancer agents and enhance their therapeutic effectiveness.

Factors affecting the feasibility of post-authorisation RCTs for conditionally authorised anticancer medicines: a multistakeholder perspective from a qualitative focus group study

ObjectiveThe collection of comprehensive data from post-authorisation trials for conditionally authorised anticancer medicines is frequently delayed. This raises questions about the feasibility of post-authorisation randomised controlled trials (RCTs) that aim...

Selective Metal‐Coordinated Nanodrugs Based on Thiazine Moiety for Anticancer Therapeutics: Spectroscopic, Theoretical, and Molecular Docking Studies

ABSTRACTThe current study involved production, comprehensive structural analysis, and physicochemical characterizing of two distinctive complexes namely, Cu(TBH) and Zn(TBH); TBH donor ligand: N′‐(1‐(3,6‐dihydro‐4‐hydroxy‐2,6‐dioxo‐2H‐1,3‐thiazin‐5‐yl)ethylidene)‐2‐hydroxybenzohydrazide) using a wide range of analytical methods, including elemental analysis, UV–Vis, FT‐IR, and 1HNMR spectrometry, molar conductivity and magnetic susceptibility measurements, and thermal analysis. According to the findings, chelation can occur through O, N, and O donor atoms of monoanionic chelator for generating mono‐nuclear chelates with tetrahedral geometry for Cu (II) and octahedral geometry for Zn (II). The anticarcinogenic ability of TBH chelator and its coordinated compounds against human liver cancer (HepG‐2) was investigated. The Cu(TBH) complex was found to have selective and promising anticancer activity against a liver cancer cell line, with lower IC50 (liver carcinoma cell line) and higher IC50 (normal human cell line) values than other produced compounds and standard drugs. Utilizing DFT computations, the molecular structures of the TBH and its complexes were verified, offering a detailed understanding of their quantum chemical characteristics. A quantitative structure–activity relationship (QSAR) model, which illustrates the association between DFT‐computed descriptors and biological activities pIC50, was also created using multiple linear regression (MLR) on the synthesized compounds as anticancer medicines. Additionally, there are no issues with the produced compounds' oral bioavailability according to (ROF) Lipinski's rule of five. Furthermore, docking studies of the synthesized TBH chelator and its chelates with CDK2 kinase have been performed to validate the biological findings. According to our findings, the novel Cu(TBH) nanodrug exhibits considerable cytotoxic activity, prompting further study into its pharmacological profile and exploring its potential in drug development.

Construction of an Innovative Nanogel and Its Applications for Achieving Chemo-Immunotherapy of Tumors.

Malignant tumors, also known as cancers, are a global public health problem. Nanogels are promising carriers for the delivery of anticancer medicines. Therefore, based on the unique microenvironment of tumor cells and the advantages of nanogels, a simple and economical one-pot synthesis method was designed to construct natural polysaccharide-based redox-responsive nanogels (LDD NGs). The enhanced permeability and retention (EPR) effect enriched LDD NGs in tumor cells, which then rapidly collapsed and released the natural antitumor drug diosgenin (DG) and the natural polysaccharide lentinan (LNT) via the depletion of a high level of reduced glutathione (GSH) in tumor cells, resulting in a synergistic therapeutic effect of chemotherapy and immunotherapy. In vivo antitumor experiments showed that LDD NGs could inhibit the proliferation and metastasis of the A549 lung cancer cells. Further studies indicated that LDD NGs could increase the production of ROS and induce apoptosis of A549 cells. In addition, LNT released from LDD NGs could promote the proliferation of dendritic cells, increase the production of NO, and upregulate the expressions of the costimulatory molecules CD40, CD80, CD86, and MHC-II. The construction of LDD NGs was a novel drug synthesis approach that could provide fresh ideas for the development of polysaccharide-based redox-responsive drug delivery systems.

In vitro and In Silico Molecular Modeling Studies of Newly Synthesized Pyrrole Derivatives for their Antimicrobial and Anticancer Properties

Background: Pyrroles are biologically active scaffolds that can have a number of different effects. They also have unique pharmacophores inside their ring system that make it easier to make molecules that are more active. Significantly, in the past ten years, research has been conducted on the anti-bacterial properties, with a particular emphasis on drug-resistant Gram-positive and Gram-negative pathogens such as mycobacteria. Additionally, scaffolds based on pyrroles were utilized in the production of anti-tumor medicines that function by modulating or suppressing genes. Objective: This research aimed to create new pyrrole derivatives by chemical means and evaluate their antimicrobial and anticancer properties. Methods: By reacting diverse 1H-pyrrole-2-carbohydrazide derivatives with benzaldehyde under normal conditions, a number of pyrrole variations were created. IR, mass spectroscopy, NMR, and elemental analysis were used to characterize the synthesized compounds. The serial dilution method was used to assess antimicrobial activity, along with a molecular docking study against the enzyme α-topoisomerase II (α-Topo II), which effectively controls the topology of DNA. This enzyme is strongly expressed in rapidly dividing cells and is crucial for transcription, replication, and chromosome structure. Pyrrole and its synthetic derivatives are known to exhibit strong anticancer activity by specifically targeting α-Topo II, which has led multiple researchers to investigate α-Topo II inhibitors as potential anticancer medicines. Consequently, designing pyrroline derivatives is interesting since the succinimide portion of the joined heteroaromatic molecule can selectively engage with the ATP binding pocket via the hydrogen bond network. Newer synthesized compounds were also docked via Schrodinger 2022-4 into the active pocket of the three-dimensional crystallographic structure of the ATP site of human topoisomerase IIα (htopo IIα) (PDB ID: 1zxm). Results: Among the newly synthesized pyrrole derivatives, compounds demonstrated significant anti- microbial activity. In addition, the AutoDock Vina application was used to perform in-silico docking computations. Compounds 1a and 1h were found to have a stronger antiproliferative effect than compounds against MCF-07 breast cancer cell linen our study, ligands 1a and 1b exhibited better binding energies of -5.049 and -5.035 kcal/mol, respectively. Most of the synthesized pyrrole derivatives showed promising antiproliferative effects; however, further in vivo investigations are needed to confirm or refute these results. Conclusion: The results of this investigation show that pyrrole derivatives have the potential to be effective antimicrobial and anticancer agents. While resolving safety issues, the structural alterations carried out in this study enhanced the compounds' medicinal capabilities. To clarify the underlying mechanisms of action and enhance the pharmacological characteristics of these new pyrrole derivatives, further research is necessary.

Investigating the availability, affordability, and market dynamics of innovative oncology drugs in Morocco: an original report.

The cost of cancer drugs presents a significant challenge to accessibility of treatment worldwide. Projections indicate that by 2040, two-thirds of cancer cases will occur in low- and middle- income countries. Paradoxically, despite this impending burden, LMICs command less than 5% share of global resources for treating cancer. Morocco, like many LMICs, faces significant obstacles in providing innovative cancer treatments to its population. Firstly, we aimed to conduct an original research investigating the availability and affordability of innovative cancer drugs in Morocco. Secondly, we sought to review the broader market dynamics, pricing, and reimbursement policies in the country. For the first objective, we identified a preliminary list of medicines approved for oncological indications in the Moroccan market based on resources from ANAM (National Agency for Health Insurance), pharmacy regulators, and online resources that compile information on approved medicines. For the second objective, we exhaustively reviewed the regulatory documents, legal texts and grey literature reports. All the informations were examined by pharma delegates and local experts. As of January 2024, Morocco has 39 innovative anticancer medicines with market authorization. 30% of these drugs were approved after 2020. The majority of approved drugs were for breast, lung, colorectal, and prostate cancer. The period between FDA approval and entry into the Moroccan market ranges from 2 to 7years, with a median of 3years for breast cancer drugs and 7years for more expensive drugs like Olaparib and Osimertinib. 22 out of the 39 drugs are not reimbursed, with an average reimbursement time of 4years. Compared to prices in France, the most notable pricing disparities concern immunotherapy agents, priced 600 to 900 euros lower in France, while drugs like Pazopanib and Erlotinib cost 50% less in Morocco. Our study reveals significant disparities in the availability and affordability of innovative cancer drugs in Morocco. Regulatory hurdles, importation challenges, and pricing strategies contribute to this inequitable landscape. Addressing systemic barriers, fostering collaborations between stakeholders, and adopting a value-based pricing approach are imperative steps toward ensuring equitable access to high-quality interventions for patients, regardless of their geographical location.

Emerging Role of Natural Topoisomerase Inhibitors as Anticancer agents

Abstract: Topoisomerases I and II are the functionally two forms of DNA topoisomerase. In anticancer research, novel anticancer chemotherapeutical capable of blocking topoisomerase enzymes have been discovered. Most commonly, topoisomerase causes replication fork arrest and doublestrand breaks, and this is how a clinically successful topoisomerase-targeting anticancer medicines work. Unfortunately, this novel mechanism of action has been linked to the development of secondary malignancies as well as cardiotoxicity. The specific binding locations and mechanisms of topoisomerase poisons have been identified by studying the structures of topoisomerase-drug-DNA ternary complexes. Recent breakthroughs in science have revealed that isoform-specific human topoisomerase II poison could be created as safer anticancer drug molecules. It may also be able to develop catalytic inhibitors of topoisomerases by focusing on their inactive conformations. In addition to this, the discovery of new bacterial topoisomerase inhibitor molecules and regulatory proteins could lead to the discovery of new human topoisomerase inhibitors. As a result, biologists, organic chemists, and medicinal chemists worldwide have been identifying, designing, synthesizing, and testing a variety of novel topoisomerase-targeting bioactive compounds. This review focused on topoisomerase inhibitors, their mechanisms of action, and different types of topoisomerase inhibitors that have been developed during the last ten years.

Synthesis, DFT, ADMET, and Docking studies of Novel Sulfonyl Piperidine Analogues containing 2,3-Dihydrobenzofuran-5-Carboxamide.

The development of effective anti-cancer medicines with low side effects is imperative as cancer continues to be a leading cause of death globally. By obstructing the survival and growth of cancer cells, small-molecule medications have made tremendous progress in the field of cancer research. Several bioactive heterocyclic compounds, including derivatives of piperidine and 2,3-dihydrobenzofuran, have shown great promise and are found in various anti-cancer medications. Cancer growth and metastasis are hindered by these small molecule inhibitors, which interfere with vital signals that drive cancer cell proliferation. This study focuses on the synthesis and evaluation of novel Sulfonyl Piperidine Analogues containing 2,3-Dihydrobenzofuran-5-Carboxamide as potential anti-- cancer agents. The synthesized compounds were characterized using spectroscopic techniques such as 1H NMR and ESI-MS. Protein-drug interaction studies, DFT analysis, and target prediction techniques were employed. The anti-cancer properties of the compounds were evaluated in vitro against MCF-7 cell lines. Compounds 5 and 7 were specifically investigated for their growth-inhibitory effects on MCF7 breast cancer cells. Compounds5 and 7 demonstrated strong binding affinity towards both mutated BRCA1 (PDB ID: 1N5O) and BRCA2 (PDB ID:8BR9). Furthermore, they displayed notable efficacy against MCF-7 cell lines. Synthesized compounds displayed activity against MCF-7 cell lines, supporting findings from in-silico predictions. Further investigations are warranted to elucidate the mechanisms of action of these selected molecules against MCF-7 cell types.

A comparative analysis of antioxidant, anti-inflammatory, and anticancer activities of the crude and fractionated extracts from Distichochlamys benenica

Abstract Distichochlamys benenica is a newly discovered plant belonging to the Distichochlamys family, which exerts many important biological activities. However, the anti-cancer, anti-inflammatory, and anti-oxidant effects of the crude (ME) and fractioned extracts of D. benenica, such as hexane (HE), chloroform (CE), and ethyl acetate extracts (EAE), have not been elucidated yet. The antioxidant activity of the extracts was evaluated via DPPH free radical scavenging and phosphomolybdate assays. The anti-inflammatory potential of the extracts was assessed via their inhibitory effects on protein denaturation and nitric oxide production. The anti-cancer effect of the extracts against A549 and MDA-MB-231 cell lines was determined via MTT assay. The results revealed that among four extracts, the polyphenol concentration was highest in EAE (350.59 ± 13.26 mg GAE/g) while the flavonoid content was highest in HE and ME. Furthermore, the greatest DPPH radical capture efficiency was demonstrated by EAE (89.76 ± 0.68%), and total antioxidant activity was greatest in HE (204.18 ± 3.51 mg AAE/g). The greatest suppression of NO generation was similarly shown by EAE and HE, with IC50 values ranging from 3.72-4.06 µg/mL, respectively. Additionally, HE and EAE exhibited an inhibitory effect on protein denaturation (ranging from 12.76%-28.81%). HE and EAE had the greatest effectiveness against MDA-MB-231 cell lines in the antitumor test. These findings validate the potent antioxidant, anti-inflammatory, and anti-cancer properties of D. benenica extracts, especially EAE and HE, and pave the way for the application of the extracts in the pharmaceutical industry as promising anti-inflammatory and anti-cancer medicines.

Pyrazole Paradigms: Unveiling Synthetic Pathways and Unraveling Anti-Cancer Potential.

This review investigates the synthetic methods and anti-cancer activities of pyrazole compounds. Various synthetic approaches, including traditional organic synthesis and microwaveassisted synthesis, have been used to change the pyrazole core structure, resulting in new compounds with improved pharmacological properties. The paper also covers the mechanisms of action that underpin pyrazole derivatives' anti-cancer characteristics, focusing on interactions with major molecular targets implicated in cancer growth and proliferation. SAR insights help to rationally develop novel anti-cancer drugs. In conclusion, the review emphasizes the versatility of pyrazole derivatives as scaffolds for the discovery and development of new anti-cancer medicines. By understanding synthesis routes and unravelling anti-cancer potential, this study hopes to encourage new research endeavours focused on leveraging the therapeutic advantages of pyrazole paradigms in the fight against cancer.

Magnetosomes as Potential Nanocarriers for Cancer Treatment.

Magnetotactic bacteria (MTBs) and their organelles, magnetosomes, are intriguing options that might fulfill the criteria of using bacterial magnetosomes (BMs). The ferromagnetic crystals contained in BMs can condition the magnetotaxis of MTBs, which is common in water storage facilities. This review provides an overview of the feasibility of using MTBs and BMs as nanocarriers in cancer treatment. More evidence suggests that MTBs and BMs can be used as natural nanocarriers for conventional anticancer medicines, antibodies, vaccine DNA, and siRNA. In addition to improving the stability of chemotherapeutics, their usage as transporters opens the possibilities for the targeted delivery of single ligands or combinations of ligands to malignant tumors. Magnetosome magnetite crystals are different from chemically made magnetite nanoparticles (NPs) because they are strong single-magnetic domains that stay magnetized even at room temperature. They also have a narrow size range and a uniform crystal morphology. These chemical and physical properties are essential for their usage in biotechnology and nanomedicine. Bioremediation, cell separation, DNA or antigen regeneration, therapeutic agents, enzyme immobilization, magnetic hyperthermia, and contrast enhancement of magnetic resonance are just a few examples of the many uses for magnetite-producing MTB, magnetite magnetosomes, and magnetosome magnetite crystals. From 2004 to 2022, data mining of the Scopus and Web of Science databases showed that most research using magnetite from MTB was carried out for biological reasons, such as in magnetic hyperthermia and drug delivery.

Role of Intermittent Fasting In Starving Cancer Cells

Introduction. An absolute burden of over 35 million new cancer cases is predicted by 2050. Although significant progress has been made in the field of oncology via the use of surgical removal, radiation treatment, chemotherapy, and the introduction of immunotherapy, the overall rates of survival and prognoses for cancer patients are still unsatisfactory. In the last decade, intermittent fasting (IF) has become increasingly popular for weight control and potential health benefits. Additionally, research has primarily focused on investigating the impact of IF on metabolism, mitochondrial function, stress responses, repair mechanisms, and autophagy. The aim of the study. To make a literature review about the role of intermittent fasting in starving cancer cells. Materials and methods. This narrative review involved a comprehensive search through databases such as PubMed and Google Scholar. Distinct keywords such as - ″intermittent fasting″, ″intermittent fasting regimens″, ″calorie restriction″, ″oncology″, ″chemotherapy″ and ″tumor microenvironment″ were used. Results. IF exhibits significant impacts on the immune system's ability to fight against tumors by strengthening the ability of hematopoietic stem cells to replenish themselves and enhance immunosuppression. Under an IF program, certain tissues and organs exhibit enhanced resilience to various stressors. Emerging research shows that IF has the potential to enhance the effectiveness and tolerance of anticancer medicines, regulate carcinogenic influences, reprogram clock genes' rhythmic expression in tumor environments, inhibit tumor growth by modifying natural processes like insulin signalling, heme oxygenase-1, prevent the proliferation of myeloid-derived suppressor cells and priming the tumor microenvironment to support drug delivery that targets tumors. Cancer treatment via IF notably shields normal cells while raising the efficacy of chemotherapy (CT) and reducing CT-induced inflammation via several immunological, biochemical, and molecular mechanisms. Conclusions. Regularly practising fasting for more than one day may confer notable health benefits by protecting healthy normal cells against the deleterious effects of chemotherapy and radiation. The synergistic therapeutic impact of intermittent fasting alongside chemotherapy on tumors suggests that it enhances the efficacy of chemotherapy while also notably reducing chemotherapy-induced inflammation. While intermittent fasting shows promise for certain cancers, such as breast cancer, its efficacy for other types remains uncertain, necessitating further research and personalized treatment plans.

Novel 1,2,3-triazole derivatives containing benzoxazinone scaffold: Synthesis, docking study, DFT analysis and biological evaluation

In order to address the drastic demand for novel broad-spectrum antibacterial and anticancer medicines with enhanced activity, computer modelling was utilized to rationally develop newer anticancer triazole based drugs. A unique series of benzo[d][1,3]oxazin-4-one linked 1,2,3-triazoles was synthesised in five steps, with good yields and an assessment of their antibacterial and anticancer activities. IR spectroscopy, 1H NMR, 13C NMR, and mass spectrometry were used to characterize the synthesis of triazole compounds. From antibacterial screening, the prepared derivatives namely, 8a, 8e, 8h and 8k showed excellent inhibitory potential against S. aureus with ZI of 28 ± 0.48, 30 ± 0.42, 30 ± 0.11, 35 ± 0.23 mm respectively, compared to moxifloxacin (33 ± 0.15 mm). Compared to doxorubicin (IC50 = 2.45 ± 0.14 μM), compounds 8h and 8k demonstrated superior and exceptional cytotoxicity against the A549 cell line (IC50 = 2.30 ± 0.26 and 1.90 ± 0.30 μM, respectively). Latter All the derivatives were further subjected to in silico docking studies against human lung (PDB: 2P85), VEGFR2 kinase domain (PDB: 3CP9) and could serve as ideal leads for additional modification in the field of anticancer research. Based on docking results, 8e showed that the amino acids Arg373(A), Gly113(A), Glu103(A), Asp108(A), Ser119(A), Asn375(A), Val374(A), Lys387(A), and Asn120(A) exhibited highly stable binding to cytochrome P4502A13 receptor of lung cancer. Furthermore, Density Functional Theory (DFT) calculations are performed to support the molecular docking studies. Compounds 8e, 8h, and 8k were discovered to have estimated energy gaps (eV) of 3.181, 4.034, and 3.539 eV, respectively. Triazole 8h exhibited the lowest chemical hardness (1.962 eV) and the highest chemical softness (0.252 eV), which also suggests that it is more reactive than all the other compounds under study. Moreover, these scaffolds physicochemical characteristics, filtration molecular properties, assessment of toxicity, and bioactivity scores were assessed in relation to ADME (absorption, distribution, metabolism, and excretion). In conclusion, we discovered a novel benzoxazinone linked 1,2,3-triazoles with promising antimicrobial and anticancer activity and a favorable pharmacokinetic profile.

Pharmacology of natural compounds found in clinical trials used for ameliorating/preventing Cancer

In the field of oncology, the use of herbal medicines as a supplemental or alternative treatment option has been generally accepted (Catharanthus roseus, Podophyllum peltatum L., Taxus brevifolia Nutt., Taxus baccata, etc.). As a result, several brand-new cytotoxic chemicals are discovered each year in plants, opening up fresh avenues for the treatment of cancer. The examination of naturally occurring molecular entities that could benefit the pharmaceutical business is a focus of many researchers. The search for clinical efficacy validation follows the discovery of drugs with anticancer activity in preclinical trials. Only 29 of the 240 anticancer medicines licensed in the previous 40 years are entirely synthetic, which could be attributed to the advantages of natural substances such as lower side effects and the ability to affect numerous Signaling pathways involved in the carcinogenesis process. In addition, synthetic compounds with natural pharmacophores that imitate the effects of natural products have been licensed as anticancer medications throughout the past ten years. Since the start of cancer research, phytochemicals have been a focal point because they were some of the first antineoplastic medicines found (e.g., leucovorin in 1950, carzinophilin in 1954, vincristine in 1963, actinomycin D in 1964, etc.). Additionally, their research is still ongoing today. It is crucial to note that natural substances are used both as adjuvants and chemotherapeutic agents in the treatment of cancer. By summarizing the three aspects of natural chemicals' anticancer action, this review offers a fresh viewpoint on their use in the field of oncology. Chemotherapeutic drugs because of their inherent antitumor effects, chemopreventive drugs, and sensitizers for multi-drug resistance are the first three categories.

Ethanolic extraction and GC-MS analysis of antioxidant and anticancer bioactive compounds from Mentha arvensis and Aegle marmelos

Bioactive components used to treat human ailments are abundant in medicinal plants. Mentha arvensis and Aegle marmelos have therapeutic properties due to the presence of many phytonutrients. Gas chromatography–mass spectrometry (GC-MS) was used to evaluate the properties of the antioxidant and anticancer bioactive components found in the ethanolic extracts of Mentha arvensis and Aegle marmelos leaves. The major constituents identified in the leaf extracts were octadecanoic acid, heptadecanoic acid, 15-methyl-9,12,15-octadecatrienoic acid, ethyl ester, hexadecanoic acid, neophytadiene, pentadecane, hexadecane, and 1-octadecanol. Some of these components have antibacterial, antioxidant, anticancer, and anti-inflammatory properties. Among the identified compounds, octadecanoic acid and n-hexadecanoic acid are pivotal for their anticancer and antioxidant effects. The GC–MS characterisation indicated the existence of abundant bioactive compounds, confirming their potential therapeutic activities. This study showed that the leaves of Mentha arvensis and Aegle marmelos could be used as novel sources of antioxidants and anticancer medicines.

Geographical and genetic clines in Dracocephalum kotschyi X Dracocephalum oligadenium hybrids: landscape genetics and genocline analyses

Conservation and management of medicinally important plants are among the necessary tasks all over the world. The genus Dracocephalum (Lamiaceae) contains about 186 perennials, or annual herb species that have been used for their medicinal values in different parts of the world as an antihyperlipidemic, analgesic, antimicrobial, antioxidant, as well as anticancer medicine. Producing detailed data on the genetic structure of these species and their response against climate change and human landscape manipulation can be very important for conservation purposes. Therefore, the present study was performed on six geographical populations of two species in the Dracocephalum genus, namely, Dracocephalum kotschyi, and Dracocephalum oligadenium, as well as their inter-specific hybrid population. We carried out, population genetic study, landscape genetics, species modeling, and genetic cline analyses on these plants. We present here, new findings on the genetic structure of these populations, and provide data on both geographical and genetic clines, as well as morphological clines. We also identified genetic loci that are potentially adaptive to the geographical spatial features and genocide conditions. Different species distribution modeling (SDM) methods, used in this work revealed that bioclimatic variables related to the temperature and moisture, play an important role in Dracocephalum population’s geographical distribution within IRAN and that due to the presence of some potentially adaptive genetic loci in the studied plants, they can survive well enough by the year 2050 and under climate change. The findings can be used for the protection of these medicinally important plant.

Anoikis-Related Long Non-Coding RNA Signatures to Predict Prognosis and Immune Infiltration of Gastric Cancer.

Anoikis is a distinct type of programmed cell death and a unique mechanism for tumor progress. However, its exact function in gastric cancer (GC) remains unknown. This study aims to investigate the function of anoikis-related lncRNA (ar-lncRNA) in the prognosis of GC and its immunological infiltration. The ar-lncRNAs were derived from RNA sequencing data and associated clinical information obtained from The Cancer Genome Atlas. Pearson correlation analysis, differential screening, LASSO and Cox regression were utilized to identify the typical ar-lncRNAs with prognostic significance, and the corresponding risk model was constructed, respectively. Comprehensive methods were employed to assess the clinical characteristics of the prediction model, ensuring the accuracy of the prediction results. Further analysis was conducted on the relationship between immune microenvironment and risk features, and sensitivity predictions were made about anticancer medicines. A risk model was built according to seven selected ar-lncRNAs. The model was validated and the calibration plots were highly consistent in validating nomogram predictions. Further analyses revealed the great accuracy of the model and its ability to serve as a stand-alone GC prognostic factor. We subsequently disclosed that high-risk groups display significant enrichment in pathways related to tumors and the immune system. Additionally, in tumor immunoassays, notable variations in immune infiltrates and checkpoints were noted between different risk groups. This study proposes, for the first time, that prognostic signatures of ar-lncRNA can be established in GC. These signatures accurately predict the prognosis of GC and offer potential biomarkers, suggesting new avenues for basic research, prognosis prediction and personalized diagnosis and treatment of GC.