Promising Anticancer Agent Research Articles

4-(Pyrazolyl)benzenesulfonamide Ureas as Carbonic Anhydrases Inhibitors and Hypoxia-Mediated Chemo-Sensitizing Agents in Colorectal Cancer Cells.

Hypoxia in tumors contributes to chemotherapy resistance, worsened by acidosis driven by carbonic anhydrases (hCA IX and XII). Targeting these enzymes can mitigate acidosis, thus enhancing tumor sensitivity to cytotoxic drugs. Herein, novel 4-(pyrazolyl)benzenesulfonamide ureas (SH7a-t) were developed and evaluated for their inhibitory activity against hCA IX and XII. They showed promising results (hCA IX: KI = 15.9-67.6 nM, hCA XII: KI = 16.7-65.7 nM). Particularly, SH7s demonstrated outstanding activity (KIs = 15.9 nM for hCA IX and 55.2 nM for hCA XII) and minimal off-target kinase inhibition over a panel of 258 kinases. In NCI anticancer screening, SH7s exhibited broad-spectrum activity with an effective growth inhibition full panel GI50 (MG-MID) value of 3.5 μM and a subpanel GI50 (MG-MID) range of 2.4-6.3 μM. Furthermore, SH7s enhanced the efficacy of Taxol and 5-fluorouracil in cotreatment regimens under hypoxic conditions in HCT-116 colorectal cancer cells, indicating its potential as a promising anticancer agent.

Synthesis and effect of 4-acetylphenylamine-based imidazole derivatives on migration and growth of 3D cultures of breast, prostate and brain cancer cells.

In this study, we have synthesized novel 4-acetophenone moiety-bearing functionalized imidazole derivatives containing S-, and N-ethyl substituents and evaluated their anticancer activity. Their anticancer activity was studied against human breast carcinoma (MDA-MB-231), human prostate carcinoma (PPC-1), and human glioblastoma (U-87). Compounds 4, 9, 14, and 22 were identified as the most promising anticancer agents from a series of imidazole derivatives. They showed the highest cytotoxicity by MTT assay against MDA-MB-231, PPC-1 and U-87 cell lines. Compounds 14 and 22 were most selective against PPC-1 and U-87 cell lines, and their EC50 values against these cell lines ranged from 3.1 to 47.2 µM. Most tested compounds showed lower activity against the triple-negative breast cancer MDA-MB-231 cell line. None of the imidazole derivatives possessed an inhibiting effect on the migration of PPC-1 and U-87 cells by 'wound' healing assay. In spheroid assay, the most promising were compounds 14 and 22, especially in PPC-1 3D cultures. They efficiently reduced both the size and the viability of PPC-1 spheroid cells.

Host defense peptides at the crossroad of endothelial cell physiology: Insight into mechanistic and pharmacological implications.

Antimicrobial peptides (AMPs), particularly host defense peptides (HDPs), have gained recognition for their role in host defense mechanisms, but they have also shown potential as a promising anticancer, antiviral, antiparasitic, antifungal and immunomodulatory agent. Research studies in recent years have shown HDPs play a crucial role in endothelial cell function and biology. The function of endothelial cells is impacted by HDPs' complex interplay between cytoprotective and cytotoxic actions as they are known to modulate barrier integrity, inflammatory response and angiogenesis. This biphasic response varies and depends on the peptide structure, its concentration, and the microenvironment. These effects are mediated through key signaling pathways, including MAPK, NF-κB, and PI3K/Akt, which controls responses such as cell proliferation, apoptosis, and migration. In the present review, we have discussed the significance of the intriguing relationship between HDPs and endothelial cell physiology which suggests it potential as a therapeutic agents for the treating wounds, cardiovascular diseases, and inflammation-related endothelial damage.

Cytotoxic and Antibacterial Activity of Koninginins Isolated from the Mangrove-Derived Endophytic Fungus Trichoderma sp.

The search for bioactive compounds for the treatment of several diseases has led to the study of endophytic fungi. Neoplastic diseases are among the most significant health concerns due to their high mortality rate, and there is a dearth of efficacious pharmaceutical agents for the treatment of cancer. Gastric cancer is one of the most aggressive forms of cancer and is among those with the highest mortality rates in Brazil. Accordingly, the objective of this study was to identify compounds with cytotoxic activity from the mangrove-derived endophytic fungus Trichoderma sp. Isolation of the chemical compounds was conducted using chromatographic methods, while structural elucidation was achieved through the application of spectroscopic (NMR and UV) and spectrometric (MS) techniques. The fungus Trichoderma sp. was found to produce five distinct koninginins (A, B, C, E, and J). The organic phases of the extracts and isolated compounds were evaluated for their antimicrobial and cytotoxic potentials, respectively, through microdilution testing and the MTT method. In the cytotoxicity assay, both the AF extract and koninginin A demonstrated favorable outcomes, indicating their potential as promising anticancer therapeutic agents.

Design, synthesis, and in vitro and in vivo biological evaluation of triazolopyrimidine hybrids as multitarget directed anticancer agents.

In response to the urgent need for new anti-proliferative agents, four novel series of triazolopyrimidine compounds (7a-e, 9a-d, 11a-f, and 13a-e) were synthesized and evaluated for in vitro anticancer efficacy against HCT116, HeLa, and MCF-7 cell lines. Compound 13c emerged as the most potent, with IC50 values of 6.10, 10.33, and 2.42 μM respectively, while 11e and 7c also showed strong activity. In multi-target suppression tests, 13c exhibited the highest inhibition against EGFR, TOP-II, HER-2, and ARO (IC50: 0.087, 31.56, 0.078, and 0.156 μM, respectively). Flow cytometry revealed 13c's ability to suppress the S-phase cell population in MCF-7 cells. In vivo studies of 13c demonstrated significant tumor growth inhibition, comparable to the positive control. Molecular docking studies supported the experimental findings, confirming the binding of the novel motifs to the target enzymes' active sites. This comprehensive evaluation highlights the potential of these triazolopyrimidine compounds, particularly 13c, as promising anticancer agents, warranting further investigation.

Thiazolopyrimidinium systems with a quaternized nitrogen atom as promising anticancer agents

Thiazolopyrimidinium systems with a quaternized nitrogen atom are attracting increasing attention in the development of new anticancer drugs. Their unique chemical structure and potential biological properties make them promising candidates for the development of effective drugs. In recent years, researches have shown that these compounds have significant activity against various types of tumors due to their ability to interact with cellular targets, disrupting processes critical for the survival and proliferation of tumor cells. This review examines the current state of researches on thiazolopyrimidines, including synthesis, mechanisms of action, and evaluation of their antitumor potential, with an emphasis on the importance of the quaternized nitrogen atom in their biological activity.

Molecular docking, DFT and antiproliferative properties of 4-(3,4-dimethoxyphenyl)-3-(4-methoxyphenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine as potent anticancer agent with CDK2 and PIM1 inhibition potency.

Due to the limited effeteness and safety concerns associated with current cancer treatments, there is a pressing need to develop novel therapeutic agents. 4-(3,4-Dimethoxyphenyl)-3-(4-methoxyphenyl)-1-phenyl-1H-pyrazolo[3,4-b]pyridine (3) was synthesized and Initially screened on 59 cancer cell lines showed promising anticancer activity, so, it was chosen for a 5-dose experiment by the NCI/USA. The GI50 values ranged from 1.04 to 8.02 μM on the entire nine panels (57 cell lines), with a GI50 of 2.70 μM for (MG-MID) panel, indicating an encouraging action. To further explore the molecular attributes of compound 3, we optimized its structure using DFT with the B3LYP/6-31 + + G(d,p) basis set. We have considered vibrational analysis, bond lengths and angles, FMOs, and MEP for the structure. Additionally, pharmacokinetic assessments were conducted using various in-silico platforms to evaluate the compound safety. A molecular modeling study created a kinase profile on 44 different kinases. This allowed us to study our compound's binding affinity to these kinases and compare it to the co-crystallized one. Our findings revealed compound 3 exhibited better binding for half of the tested kinases, suggesting its potential as a multi-kinase inhibitor. To further validate our computational results, we tested compound 3 for its inhibitory effects on CDK2 and PIM1. Compound 3 exhibited an IC50 of 0.30 µM for CDK2 inhibition, making it five times less active than Roscovitine, which has an IC50 of 0.06 µM. However, compound 3 demonstrated slightly better inhibition of PIM1 compared to Staurosporine. These findings suggest that compound 3 is a promising anticancer agent with the potential for further development into a highly active compound.

Repurposing the antipsychotic drug penfluridol for cancer treatment (Review).

Cancer is one of the most prevalent diseases and the leading cause of death worldwide. Despite the improved survival rates of cancer in recent years, the current available treatments often face resistance and side effects. Drug repurposing represents a cost‑effective and efficient alternative to cancer treatment. Recent studies revealed that penfluridol (PF), an antipsychotic drug, is a promising anticancer agent. In the present study, a scoping review was conducted to ascertain the anticancer properties of PF. For this, a literature search was performed using the Scopus, PubMed and Web of Science databases with the search string 'penfluridol' AND 'cancer'. A total of 23 original articles with in vivo and/or in vitro studies on the effect of PF on cancer were included in the scoping review. The outcome of the analysis demonstrated the anticancer potential of PF. PF significantly inhibited cell proliferation, metastasis and invasion while inducing apoptosis and autophagy in vivo and across a spectrum of cancer cell lines, including breast, lung, pancreatic, glioblastoma, gallbladder, bladder, oesophageal, leukaemia and renal cancers. However, research on PF derivatives with high anticancer activities and reduced neurological side effects may be necessary.

Potential Anti-tumor Effects and Apoptosis-Inducing Mechanisms of Saponins: A Review.

The search for effective cancer therapies highlights saponins, natural plant-derived compounds, as promising anticancer agents. These compounds induce apoptosis in cancer cells by activating caspases, essential enzymes for cell death. For example, Soyasapogenol B from Glycine max and Astragaloside IV from Astragalus membranaceus effectively trigger apoptosis in cancer cells. Additionally, saponins, such as Compound K from American ginseng and Saikosaponin from Bupleurum falcatum, affect extrinsic and intrinsic pathways, including mitochondrial release of cytochrome C and activation of caspase-9. Ziyuglycoside II also acts on both pathways and activates the ROS/JNK pathway. Understanding these mechanisms provides promising prospects for developing more specific and safer anticancer therapies. The review utilized the ScienceDirect, PubMed, and Google Scholar databases. It was found that original articles and reviews from journals indexed in these sources emphasized the antitumor capabilities of saponins and discussed their role in apoptosis induction and caspase activation. The activation of caspases by saponins in the apoptotic pathway involves two main pathways: the extrinsic pathway is initiated by external signals that activate caspase-8, while the intrinsic pathway starts with internal stimuli, causing the release of cytochrome c and the activation of caspase-9. These pathways both lead to the activation of effector caspases (caspases 3, 6, and 7), culminating in apoptosis, an essential process for maintaining cellular balance and eliminating damaged cells. Identifying saponins in the context of cancer and their mechanisms of action is an ever-evolving field. Future research may lead to more targeted and personalized therapies, highlighting the collaboration between basic and clinical research in this promising area of medicine.

Family Malvaceae: a potential source of secondary metabolites with chemopreventive and anticancer activities supported with in silico pharmacokinetic and pharmacodynamic profiles.

Cancer is the second most widespread cause of mortality following cardiovascular disorders, and it imposes a heavy global burden. Nowadays, herbal nutraceutical products with a plethora of bioactive metabolites represent a foundation stone for the development of promising chemopreventive and anticancer agents. Certain members of the family Malvaceae have traditionally been employed to relieve tumors. The literature concerning the chemopreventive and anticancer effects of the plant species along with the isolated cytotoxic phytometabolites was reviewed. Based on the findings, comprehensive computational modelling studies were performed to explore the pharmacokinetic and pharmacodynamic profiles of the reported cytotoxic metabolites to present basis for future plant-based anticancer drug discovery. All the available information about the anticancer research in family Malvaceae and its cytotoxic phytometabolites were retrieved from official sources. Extensive search was carried out using the keywords Malvaceae, cancer, cytotoxicity, mechanism and signalling pathway. Pharmacokinetic study was performed on the cytotoxic metabolites using SWISS ADME model. Acute oral toxicity expressed as median lethal dose (LD50) was predicted using Pro Tox 3.0 web tool. The compounds were docked using AutoDock Vina platform against epidermal growth factor receptor (EGFR kinase enzyme) obtained from the Protein Data Bank. Molecular dynamic simulations and MMGBSA calculations were performed using GROMACS 2024.2 and gmx_MMPBSA tool v1.5.2. One hundred forty-five articles were eligible in the study. Several tested compounds showed safe pharmacokinetic properties. Also, the molecular docking study showed that the bioactive metabolites possessed agreeable binding affinities to EGFR kinase enzyme. Tiliroside (25), boehmenan (30), boehmenan H (31), and isoquercetin (22) elicited the highest binding affinity toward the enzyme with a score of -10.4, -10.4, -10.2 and -10.1Kcal/mol compared to the reference drug erlotinib having a binding score equal to -9Kcal/mol. Additionally, compounds 25 and 31 elicited binding free energies equal to -42.17 and -42.68Kcal/mol, respectively, comparable to erlotinib. Overall, the current study presents helpful insights into the pharmacokinetic and pharmacodynamic properties of the reported cytotoxic metabolites belonging to family Malvaceae members. The molecular docking and dynamic simulations results intensify the roles of secondary metabolites from medicinal plants in fighting cancer.

Curcumin: A Potential Weapon in the Prevention and Treatment of Head and Neck Cancer.

Head and neck cancers (HNC) are aggressive, difficult-to-treat tumors that can be caused by genetic factors but mainly by lifestyle or infection caused by the human papillomavirus. As the sixth most common malignancy, it presents a formidable therapeutic challenge with limited therapeutic modalities. Curcumin, a natural polyphenol, is appearing as a promising multitarget anticancer and antimetastatic agent. Numerous studies have shown that curcumin and its derivatives have the potential to affect signaling pathways (NF-κB, JAK/STAT, and EGFR) and molecular mechanisms that are crucial for the growth and migration of head and neck tumors. Furthermore, its ability to interact with the tumor microenvironment and trigger the immune system may significantly influence the organism's immune response to the tumor. Combining curcumin with conventional therapies such as chemotherapy or radiotherapy may improve the efficacy of treatment and reduce the side effects of treatment, thereby increasing its therapeutic potential. This review is a comprehensive overview that discusses both the benefits and limitations of curcumin and its therapeutic effects in the context of tumor biology, with an emphasis on molecular mechanisms in the context of HNC. This review also includes possibilities to improve the limiting properties of curcumin both in terms of the development of new derivatives, formulations, or combinations with conventional therapies that have potential as a new type of therapy for the treatment of HNC and subsequent use in clinical practice.

EGCG enhances antitumor effect of apatinib in nonsmall cell lung cancer by targeting VEGF signaling to inhibit glycolysis.

Nonsmall cell lung cancer (NSCLC), one of the most aggressive malignancies globally, is characterized by poor prognosis and limited life expectancy. Epigallocatechin-3-gallate (EGCG), a natural polyphenol found in green tea, has emerged as a promising anticancer agent due to its potent antitumor properties. However, the role and the underlying mechanisms of EGCG in NSCLC remain poorly understood. Hence, this research aimed to explore the effect of EGCG on the antitumor effect of apatinib in NSCLC throughvascular endothelial growth factor(VEGF)-regulated glycolysis. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine staining, wound healing, transwell, terminal deoxynucleotidyl transferase dUTP nick-end labeling, and flow cytometry assays were carried out to evaluate the proliferation, migration, invasion, and apoptosis of H1299 cells, respectively. Furthermore, western blot analysis was used to detect the expressions of VEGF, p-vascular endothelial growth factor receptor-2, hypoxia-inducible factor 1α, neuropilin-1, phosphorylated-phosphatidylinositol 3-kinase, and phosphorylated-AKT. The transfection efficiency of H1299 cells with VEGF overexpression plasmid was also assessed by western blot analysis. Glycolysis was analyzed by estimating extracellular acidification rate, lactate concentration, glucose uptake, and the expressions of lactate dehydrogenase A, pyruvate kinase M2, and hexokinase 2. The results demonstrated that VEGF activated glycolysis in NSCLC cells. EGCG alone and apatinib alone or in combination inhibited cell viability, proliferation, invasion, migration, and glycolysis whereas promoted apoptosis in NSCLC cells. EGCG regulated glycolysis levels in NSCLC through VEGF overexpression, and enhanced the antitumor effect of apatinib in NSCLC through VEGF-regulated glycolysis. Taken together, EGCG strengthened the protective effects of apatinib in NSCLC through glycolysis mediated by VEGF.

In Silico Investigation of Taurodispacamide A and Strepoxazine A from Agelas oroides S. as Potential Inhibitors of Neuroblastoma Targets Reveals Promising Anticancer Activity

In Silico Investigation of Taurodispacamide A and Strepoxazine A from Agelas oroides S. as Potential Inhibitors of Neuroblastoma Targets Reveals Promising Anticancer Activity

Aucubin Induces Apoptotic Cell Death Through Caspase-dependent Pathways in Human Osteosarcoma MG-63 Cells

Background Osteosarcomas (OSs) are predominantly generated by mesenchymal cells, which commonly develop in the distal and upper regions of the bones. OS has high mortality rates and treatment failures, mostly due to the presence of lung metastases. Purpose The present work aimed to scrutinize the anticancer potentials of aucubin against OS human osteosarcoma (MG-63) cells. Methods The proliferation of the control and aucubin-treated MG-63 cells was studied by an XTT assay. Various fluorescent staining assays were done to assess the endogenous reactive oxygen species (ROS) accumulation and apoptosis in the aucubin-treated MG-63 cells. The caspase-3, -8, and -9 activities were investigated using the assay kits. Results The XTT assay results confirmed that the aucubin treatment considerably reduced the MG-63 cells. The findings of the various fluorescent staining assays evidenced that the aucubin treatment remarkably promoted endogenous ROS accumulation and apoptosis in the OS cells. The caspase activities were also improved in the OS cells after the aucubin treatment. Conclusion The results of this work show that aucubin treatments inhibit cell proliferation and trigger apoptosis in MG-63 cells, suggesting its potential as a promising anticancer agent. These findings will facilitate the future development of aucubin as a talented anticancer agent to treat OS.

A Dual Action Platinum(IV) Complex with Self-assembly Property Inhibits Prostate Cancer through Mitochondrial Stress Pathway.

Platinum(IV) prodrugs are highly promising anticancer agents because they can selectively target tumors and minimize the adverse effects associated with their PtII congeners. In this study, we synthesized dual action PtIV complexes by linking oxoplatin with lithocholic acid. The synthesized compounds, designated as PL-I, PL-II, and PL-III, can spontaneously self-assemble in water, resulting in the formation of spherical shape nanoparticles. Among the developed complexes, PL-III appeared to be the most potent compound against all the tested cancer cell lines, with 10 fold higher cytotoxicity compared to cisplatin in PC3 cells. The complex arrests the cell cycle in the S and G2 phases and induces DNA damage. Additional mechanistic investigations demonstrate that PL-III predominantly localizes within the mitochondria and cytoplasm. Consequently, PL-III disrupts mitochondrial membrane potential, increases ROS production, and perturbs mitochondrial bioenergetics in PC3 cells. The complex induces apoptosis through the mitochondrial pathway by upregulating pro-apoptotic protein expression and downregulating anti-apoptotic protein expression from the BCl-2 protein family. These results demonstrate that higher cellular uptake and reduction of PL-III by biological reductants in PC3 cells resulted in a synergistic effect of lithocholic acid and cisplatin, which can be easily observed due to its unique cytotoxic mechanism. This further underscores the significance of dual-action PtIV complexes in enhancing the efficacy of cancer therapy.

Ni(II)-selenosemicarbazones complexes as promising anticancer and anti-tubercular agents: Synthesis, characterization, molecular docking and binding studies with HSA and ct-DNA

Reaction of nickel(II) acetate with selenosemicarbazones (2-HOxsesc, 3-MeHOxsesc, 6-ClHOxsesc, 3-HIndsesc, 3-AcHIndsesc, 9-HAnsesc, 1-HNapsesc, 2-HNapsesc) in 1:2 (M:L) molar ratio yielded complexes of formula, [Ni(sesc)2] 1–8 (sesc = 2-Oxsesc 1, 3-MeOxsesc 2, 6-ClOxsesc 3, 3-Indsesc 4, 3-AcIndsesc 5, 9-Ansesc 6, 1-Napsesc 7, 2-Napsesc 8).Complexes are characterized using elemental analysis, FTIR, NMR (1H and 13C) spectroscopy and Mass spectrometry. The full optimized energy for 2-HOxsesc and its complex was found through Density Functional Theory calculation using B3LYP level and predicted geometry parameters are compared with literature. Selenosemicarbazones and their complexes were tested for their anti-tuberculosis activity against M. tuberculosis H37RV strain and anticancer activity against PA-1 and DU145cell lines. The anti-TB activity of 3-AcHIndsesc (MIC = 25 μg/mL) got exceptionally enhanced on complexation with Ni(II) (complex 5, MIC = 0.8 μg/mL). Anticancer activity of ligands have got enhanced on complexation with Ni(II) metal ion and best results were obtained in case of complex 5 (PA-1, IC50 =1.28; DU145, IC50 =3.83). The binding constant of 6.5 × 103M-1 and 3 × 104M−1 obtained from absorption spectroscopy (UV–Vis) indicates strong binding of complex 5 with HSA and ct-DNA. The molecular interaction of 3-AcHIndsesc and complex 5 with mycobacterium tuberculosis enoyl reductase and DNA (PDB ID: 1BNA) were checked with docking studies. The docking studies with mycobacterium tuberculosis enoyl reductase and DNA (PDB ID: 1BNA) gave minimum binding energy of -8.9 Kcal/mol and -7.5 Kcal/mol respectively for complex 5. The docking results are in well agreement with experimental data.

Computational quest, synthesis and anticancer profiling of 3-methyl quinoxaline-2-one-based active hits against the tyrosine kinase

BackgroundCancer is the predominant cause of mortality and a remarkable obstacle to elevating life anticipation in every nation on globe. Hepatocellular carcinoma (HCC), a hyper-vascular tumour, develops and progresses due to angiogenesis, a key feature of malignancy. HCC exhibits high neoangiogenic activity because of the need to generate new blood vessels for tumour growth.MethodsThe present work includes the construction of virtual library of ligands, virtual screening using the Dockthor-VS server, ADMET study using the SwissADME and Osiris property explorer. All the synthesized compounds were characterized by UV, IR, NMR and mass spectroscopic techniques. MTT assay was done to find the IC50 of the synthesized compounds against HepG2 cell line. The more active compound found is subjected to the molecular dynamics simulation study.ResultsThe ligands exhibited good docking scores, ADMET profile compared to the reference drugs. The target compounds were obtained with the satisfactory yields of 66–82%. The best activity against the HepG2 cancer cell line is observed with the compound SA-4 with IUPAC name (2-(3-methyl-2-oxoquinoxalin-1(2H)-yl)-N-(5-(3-nitrophenyl)-5H-thiazolo[4,3-b] [1,3,4] thiadiazol-2-yl) acetamide). The experimental results obtained show correlation with the in silico results. MD simulation of the compound SA-4 indicates the moderate stability of the protein-ligand complex in real time environment.ConclusionThe results obtained suggest that the compound SA-4 has the potential to be a promising anticancer agent effective against the VEGFR-2 and FGFR-4.Graphical abstract

Cytotoxic Effect of Bajong LN Rice Methanol Extract on Human Squamous Cell Carcinoma, ORL-48

Oral squamous cell carcinoma (OSCC), a major oral cancer, significantly challenges treatments and impacts patient quality of life; current therapies often cause severe side effects, highlighting the urgent need for gentler alternatives. Rice stands as one of the primary cereal grains providing the daily caloric intake for more than half of the global population. Extensive research has demonstrated the significant health benefits derived from rice, attributed to its abundance of bioactive compounds. This study endeavours to explore the potential cytotoxic effects of Bajong LN rice, a pigmented purple rice indigenous to Sarawak, on human squamous cell carcinoma, ORL-48 cells. Cells were cultured in complete DMEM/F-12 media and incubated under standard culture conditions. Upon reaching 80% confluency, the cells were treated to varied concentrations (ranging from 0 μg/ml to 2000 μg/ml) of Bajong LN rice methanol extract (BLN-ME) and cisplatin. Subsequently, the cells were incubated for 48 and 72 hours, and their cytotoxicity was assessed using the MTS assay. Results demonstrated that cisplatin inhibited ORL-48 cells with an IC50 of 7.483 μg/ml and 3.877 μg/ml; and an IC80 of 40.649 μg/ml; and 17.543 μg/ml for 48 and 72 hours, respectively. Correspondingly, BLN-ME exhibited a notable cytotoxic effect against ORL-48 cells at 48- and 72-hour intervals, with an IC50 of 354.4 μg/ml and 342.0 μg/ml; and an IC80 of 450.3 μg/ml and 423.63 μg/ml, respectively. The cytotoxic activity of BLN-ME against ORL-48 cells was observed in both a time and dose-dependent manner. Morphological analysis and the Trypan blue exclusion assay corroborated the MTS assay's findings. Our preliminary findings provide the first scientific evidence of the cytotoxic effect of BLN-ME specifically against human squamous cell carcinoma, ORL-48 cells. This study suggests the potential of BLN-ME as a promising anti-cancer agent, presenting opportunities for further investigation into its underlying cytotoxic mechanisms.

Molecular Networking-Guided Discovery of a New Antitumor Pyranonaphthoquinone from Streptomyces tanashiensis DSM 731: Insights from Single-Molecule Stretching Assays.

Guided by molecular networking based on single-molecule stretching assay, an unprecedented pyranonaphthoquinone, methyl kalafunginate (1) and five known compounds 2-6 were isolated from Streptomyces tanashiensisDSM 731. Compound 1 was characterized through a combination of spectroscopic techniques, including 1D and 2D NMR analysis, ECD calculation, and X-ray crystallography. Interestingly, we discovered that compound 1 was spontaneously converted from kalafungin (4) in methanol solution. All isolated compounds were assessed for their cytotoxic potential against a panel of five human cancer cell lines: A549, HepG2, BxPC-3, SW620, and C4-2B. Compounds 1, 2, 4, and 5 exhibited remarkable cytotoxicity with IC50values below 2.382 μM, suggesting their potential as promising anticancer agents. These findings highlight the significance of using a combined approach of single-molecule stretching assays and molecular networking for efficiently discovering novel natural products with potential therapeutic applications.

Review on Thiazolo-triazole as a Promising Anticancer Agent

Thiazolo-Triazole is a fused ring heterocyclic system consisting of three nitrogen atoms and one Sulphur atom shows wide range of biological activities. Cancer is the second leading cause of death worldwide. In past few decades, there has been a crucial necessity for the design and development of innovative anticancer drugs that can diminish the serious health problems and unwanted side effects associated with presently used anticancer drugs. Many anticancer drugs are commercially accessible, but nonexistence of selectivity, target specificity, cytotoxicity, and development of resistance lead to serious side effects. Several experiments have been going on to develop compounds with negligible or no side effects. The thiazole and triazole heterocyclic are well-recognized to possess abundant pharmacological activities, including predominantly anticancer, as revealed by various investigations on anticancer compounds and the latest research findings pointed out that to study the anticancer potential of thiazolo-triazole compounds in single scaffold.