Standard Anticancer Drugs Research Articles

Identification of Anti-Inflammatory and Anti-Cancer Compounds Targeting the NF-κB-NLRP3 Inflammasome Pathway from a Phytochemical Library of the Sideritis Genus

Ethnobotanical relevanceFor centuries, the aerial parts of Sideritis species have been known for their medicinal properties as herbal teas. Although the antioxidant and anti-inflammatory properties of the genus have been widely documented, the underlying mechanisms are yet to be sufficiently clarified. Aim of the studyWe investigated the anti-inflammatory and anticancer activities of phytochemicals of the Sideritis genus. Material and methodsThrough literature mining, a chemical library containing 657 components of the Sideritis genus was formed. We studied these compounds for binding to NLRP3 and NF-κB proteins in silico by virtual drug screening and molecular docking, and in vitro by microscale thermophoresis (MST). Liquid chromatography-high-resolution mass spectrometry analysis (LC-HRMS) was performed in the Sideritis extracts. One of the identified compounds, verbascoside, was investigated for its cytotoxic activity by mining a panel of 49 tumor cell lines in the data repository of the National Cancer Institute (NCI, USA). ResultsVirtual screening and molecular docking results highlighted two compounds targeting both proteins of interest, i.e., verbascoside (acteoside) and apigenin 7,4′-bis(trans-p-coumarate), as both had lowest binding energies of less than -10 kcal/mol. Using MST, we then verified that both compounds bound to the target proteins. Verbascoside bound to NLRP3 and NF-κB with Kd values of 0.67 ± 0.18 μM and 0.01 ± 0.08 μM, while apigenin 7,4′-bis(trans-p-coumarate) had Kd values of 4.60 ± 1.66 μM and 0.27 ± 0.75 μM, respectively. Verbascoside was abundant in the Sideritis extracts, according to LC-HRMS analysis. Since inflammation is strongly related to carcinogenesis, we investigated the anticancer activity of verbascoside in the second part of this study. We investigated the activity of verbascoside in 49 tumor cell lines of the NCI. Comparing its activity with 81 standard anticancer drugs revealed numerous interactions with DNA-damaging agents (alkylators, topoisomerase I/II inhibitors, antimetabolites), indicating that verbascoside may also affect the DNA of tumor cells. We further investigated the involvement of verbascoside in several main drug resistance mechanisms, i.e., ABC transporters, oncogenes, tumor suppressors, cellular proliferation rates, and other parameters. Except for the correlation to the mutational status of NRAS, no other significant relationships were found, indicating that verbascoside is not involved in most of the common drug resistance mechanisms. Two-dimensional cluster analysis-based heatmap generation of a proteomic profile from 40 out of 3171 proteins revealed a significant correlation between the expression of these proteins in 49 tumor cell lines, and the cellular response to verbascoside. This indicates that the presence of these proteins is a determinant for sensitivity or resistance to this natural product. ConclusionThe database established here represents a valuable resource for the screening of bioactivites of the Sideritis genus. The experimental validation of the anti-inflammatory and cytotoxic activities of selected compounds proved that virtual drug screening and molecular docking are suitable tools for the identification of putative drug candidates. Verbascoside was among the top 10 compounds binding to two key anti-inflammatory proteins, NLRP3 and NF-kB. Additionally, data from the NCI indicate that verbascoside is not linked to main drug resistance mechanisms.

Effect of Amygdalin on Murine Melanoma Cancer Cell Line and Normal Human Fibroblast Cells

Background and Objectives: Melanoma is the most aggressive and fatal type of skin cancer caused by the uncontrolled proliferation of melanocytes. The ineffectiveness of existing therapies has encouraged researchers to use herbal medicines. Amygdalin is a natural cyanogenic glycoside that is found in fruits and seeds of different plants and has antiproliferative, antioxidant, and immune-regulating activities. In this study, we aim to evaluate the effect of amygdalin against murine melanoma cancer cell line and normal human fibroblast cells. Methods: The murine melanoma cancer cell line (B16F10) and human foreskin fibroblasts (HFF) cells were exposed to different concentrations of amygdalin and dacarbazine (a standard anticancer drug) for 24 and 48 hours. The half-maximal inhibitory concentration (IC50) of amygdalin was obtained using the MTT assay and analyzed in GraphPad Prism and Excel applications. Results: Amygdalin had a high cytotoxic effect on the melanoma cell line within 48 hours of exposure, which is comparable to the cytotoxicity of dacarbazine at the same time. Amygdalin had no cytotoxic effect on HFF cells, while dacarbazine caused a high toxicity on HFF cells. Conclusion: Amygdalin, by inhibiting the proliferation of cancer cells in a dose-dependent manner, may prevent the adverse effects of chemical drugs on healthy cells and can be an appropriate treatment option for melanoma.

The Growth Inhibition Effect of Different Extracts of Taraxacum Peregrinum Leaves on Breast Cancer Cell Line MDA-MB-468

Background and Objectives: The dandelion plant (Taraxacum officinale) is one of the plants with beneficial effects. In this study, we evaluated the growth inhibition of different extracts of Iranian dandelion (Taraxacum peregrinum) on breast cancer cells. Methods: Ethanolic, methanolic, hydroalcoholic, and aqueous extracts and juice of dandelion leaves were first prepared by the Maceration method. Seven concentrations (0.01, 0.1, 1, 10, 100, 1000, and 10000 mg/mL) were prepared from different extracts. Cisplatin was used as a standard anticancer drug. Their half-maximal inhibitory concentration (IC50) values were evaluated by the MTT assay. Data analysis was done in Excel and GraphPad Prism 8.0.2 software. Results: By increasing the concentration of different extracts, the growth inhibitory effect on cancerous cells increased after 72 hours of exposure. The greatest growth inhibition effect was shown by ethanolic extract (IC50=0.75±0.31 mg/mL) after 72 hours of exposure followed by methanolic extract (IC50=6.25±0.76 mg/mL) and aqueous extract (IC50=6.59±0.94 mg/mL). Their effects were much more significant and better than Cisplatin (IC50=42.57±1.73 mg/mL). However, hydroalcoholic extract and juice of dandelion leaf did not show a significant growth inhibition effect. Conclusion: Given the significant effects of ethanolic, methanolic, and aqueous extracts of Taraxacum peregrinum leaves on inhibiting the growth of the MDA-MB-468 breast cancer cell line, this plant can be used as an herbal supplement for the treatment of breast cancer.

New Cytotoxic α‐Aminoacylamide and bis‐1,5‐Disubstituted Tetrazole Adducts From Amino‐Diterpene Molecules by Ugi Reaction

ABSTRACTIn search for new molecules of diterpene origin with promising anticancer activity, two amino‐derivatives (methyl maleopimarate aminoimide and methyl 1β,13‐epoxydihydroquinopimarate C4‐hydrazone) were involved in the 4‐component Ugi reaction (Ugi‐4CR) and pseudo‐7‐component azido‐Ugi condensation (azido‐Ugi‐7CR) to afford a series of adducts holding α‐aminoacylamide and bis‐1,5‐disubstituted tetrazole substituents. The NCI‐60 cancer cell panel screening revealed diterpene‐type Ugi adducts 2, 5, and 6 with strong antiproliferative potency with GI50 in range of 1.2–15.4 μM. The high positive correlations with standard anticancer drugs suggest microtubules or progesterone and androgen receptors as possible targets of the synthesized compounds.

A Review on Synthesis and Biological Activities of 2‐Aminophenol‐Based Schiff Bases and Their Transition Metal Complexes

ABSTRACT2‐Aminophenol‐based Schiff bases and their metal complexes have drawn a lot of interest because of their wide range of biological activity and their uses in several fields. These Schiff bases are synthesized through the condensation of 2‐aminophenol and various carbonyl compounds, and metal complexes formed easily by coordinating Schiff bases with transition metal ions possess a wide range of intriguing properties that have rendered them promising candidates in biomedical research. These compounds have a diverse array of captivating biological properties including antibacterial, antifungal, anticancer, and antioxidant actions. Their versatile nature and potential for tailored modifications hold the promise for innovative biomedical applications. Compared to standard antibiotics and other studied compounds, C2, C8–C11, and C116 complexes, along with L16 and L17 ligands, exhibit the highest antibacterial activity, while C3 and C115 complexes demonstrate the highest antifungal activity. The metal chelate formation of the ligands enhanced the antimicrobial activity by increasing their lipophilic nature. C66, C76, and C112 complexes and L39 ligand showed higher anticancer activity than standard anticancer drugs. The metal complexes have higher anticancer activity than the ligand due to improved permeability and cellular uptake. The anticancer activity of the complexes is related to the substituents of the Schiff base ligands. In compounds containing an electron‐withdrawing group (e.g., Cl or Br or NO2), the activity is obviously better than others. Ligands L1–L3 and L5, L6, and L32 demonstrated the most potent antioxidant activity, surpassing both metal complexes and standard conventional antioxidants. The ligands showed greater antioxidant activity than the metal complexes due to their capability of donating free protons to scavenge free radicals. More study is needed to fully explore the potential of 2‐aminophenol‐based Schiff bases and their transition metal complexes for the development of new drugs. This review summarizes different synthetic methods, biological activities, and the structure–activity relationship. This study aims to conduct further research on 2‐aminophenol‐based Schiff bases and their metal complexes.

Novel Nickel(II) complex bearing acenaphthenequinone based thiosemicarbazone bis-Schiff Base: Synthesis, characterization, linkage isomers, antitumor activity, DFT, and DNA docking simulation

The synthesis of a new nickel(II) coordination complex bearing acenaphthenequinone bis(thiosemicarbazone), [NiL], a N2S2 tetradentate bis-Schiff base ligand (H2L), under reflux and sonochemical conditions is reported. These new compounds (H2L and [NiL]) have been characterized by using various techniques such as FT-IR, 1H NMR, ESI-Mass spectrometry, UV–Vis, TGA, and elemental analysis. In addition, molecular structure of the ligand, (H2L)2.4DMSO.H2O, and complexes [NiL]3.2.5CH3OH.0·5H2O (1) and [NiL].CH3CN (2) have been determined by single crystal X-ray diffraction studies. The molecular structures of the nickel(II) complexes (1 and 2) revealed that they are structural isomers differing in their chelate ring arrangements (symmetric 5–5–5-trichelate system for 1 and asymmetric 4–6–5-trichelation for 2). In addition, the anticancer activity of H2L and its nickel(II) complex, [NiL], have been evaluated against human breast cancer cell line (MCF-7) using colorimetric 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The cytotoxicity of both compounds was compared with two standard anticancer drugs, cisplatin and oxaliplatin. Density functional theory (DFT) calculations were done to predict the chemical reactivity of H2L and complexes 1 and 2. Furthermore, DNA binding with H2L and [NiL] was performed using docking simulation to reveal that acenaphthenequinone and amine groups in thiosemicarbazone moieties in both ligand and complex are responsible for the groove binding to DNA via the formation of hydrogen, pi-anion, and pi-sigma bonds.

Doxorubicin encapsulated blend of sitagliptin-lignin polymeric drug delivery system for effective combination therapy against cancer

In this research, a sitagliptin-lignin biopolymer (SL) containing zinc selenide quantum dots (ZnSe QDs) and doxorubicin (doxo) was synthesized. The fabricated polymeric drug delivery system was characterized via FTIR, XRD, SEM, TGA, IR, and DSC. SLQD-Doxo exhibited an irregular surface with a 32 nm diameter and well-defined surface chemistry. Drug loading efficiency was assessed at different concentrations, pH levels, time intervals, and temperatures, and drug kinetics were calculated. Maximum drug release was observed at 6 μmol concentration after 24 h, pH of 6.5 and 45 °C. The maximum drug encapsulation efficiency was 81.75 %. SLQD-Doxo demonstrated 24.4 ± 1.04 % anti-inflammatory activity, and the maximum lipoxygenase inhibition in a concentration-dependent manner was 71.45 ± 2.02 %, compared to indomethacin, a standard anticancer drug. The designed system was applied to breast cancer MCF-7 cells to evaluate anticancer activity. Cytotoxicity of SLQD-Doxo resulted in 24.48 ± 1.64 dead cells and 74.39 ± 4.12 viable cells. Lignin's polyphenolic nature resulted in good antioxidant activity of LLQD-Doxo. The combination of SLQD-Doxo was appropriate for drug delivery at high temperatures and acidic pH of tumor cells compared to healthy cells.

Natural product inspired diastereoselective synthesis of sugar-derived pyrano[3,2-c]quinolones and their in-silico studies

Herein, we report the development of a diastereoselective and efficient route to construct sugar-derived pyrano[3,2-c]quinolones utilizing 1-C-formyl glycal and 4-hydroxy quinolone annulation. This methodology will open a route to synthesize nature inspired pyrano[3,2-c]quinolones. This is the first report for the stereoselective synthesis of sugar-derived pyrano[3,2-c]quinolones, where 100% stereoselectivity was observed. A total of sixteen compounds have been synthesized in excellent yields with 100% stereoselectivity. The molecular docking of the synthesized novel natural product analogues demonstrated their binding modes within the active site of type II topoisomerase. The results of the in-silico studies displayed more negative binding energies for the all the synthesized compounds in comparison to the natural product huajiosimuline A, indicating their affinity for the active pocket. Ten out of the sixteen novel synthesized compounds were found to have comparative or relatively more negative binding energy in comparison to the standard anti-cancer drug, doxorubicin. Additionally, the scalability and viability of this protocol was illustrated by the gram scale synthesis.

EB1089 Increases the Antiproliferative Response of Lapatinib in Combination with Antiestrogens in HER2-Positive Breast Cancer Cells.

HER2-positive breast cancer is associated with aggressive behavior and reduced survival rates. Calcitriol restores the antiproliferative activity of antiestrogens in estrogen receptor (ER)-negative breast cancer cells by re-expressing ERα. Furthermore, calcitriol and its analog, EB1089, enhance responses to standard anti-cancer drugs. Therefore, we aimed to investigate EB1089 effects when added to the combined treatment of lapatinib and antiestrogens on the proliferation of HER2-positive breast cancer cells. BT-474 (ER-positive/HER2-positive) and SK-BR-3 (ER-negative/HER2-positive) cells were pre-treated with EB1089 to modulate ER expression. Then, cells were treated with EB1089 in the presence of lapatinib with or without the antiestrogens, and proliferation, phosphorylation array assays, and Western blot analysis were performed. The results showed that EB1089 restored the antiproliferative response to antiestrogens in SK-BR-3 cells and improved the inhibitory effects of the combination of lapatinib with antiestrogens in the two cell lines. Moreover, EB1089, alone or combined, modulated ERα protein expression and reduced Akt phosphorylation in HER2-positive cells. EB1089 significantly enhanced the cell growth inhibitory effect of lapatinib combined with antiestrogens in HER2-positive breast cancer cells by modulating ERα expression and Akt phosphorylation suppression. These results highlight the potential of this therapeutic approach as a promising strategy for managing HER2-positive breast cancer.

In-silico Approach to Investigate the Phytochemicals of Terminalia arjuna as Multitarget Inhibitors of Proteins Involved with Lung Cancer

Background: Existing medications for treating cancer are reported to exhibit severe side effects, therefore, there is an urgent need to address these unprecedented health risks. With the advancements in ethnobotanical studies and research on phytochemicals, information on several medicinal plants is being revisited nowadays. Terminalia arjuna is a widely used medicinal plant in ayurvedic and Unani medicine for curing several diseases. Although the bioactives from this plant are reported to possess anticarcinogenic, antiproliferative and antioxidant activities, information on the potentials of its specific phytoconstituents on the inhibition of receptor molecules associated with lung cancer is scarce. Objectives: The primary goal of this study is to virtually screen the phytochemicals of Terminalia arjuna as potential drug candidate molecules for lung cancer. Considering all major reported receptor molecules that inevitably take part in lung cancer, it highlights the phytochemicals as novel multitargeted inhibitors of proteins responsible for lung cancer. Methods: A thorough literature review was done to select twenty-seven receptor molecules associated with lung cancer cases. The molecular docking study using PyRx predicts protein-ligand interactions and identifies potential drug targets. Evaluating the ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties of the phytochemicals present in Terminalia arjuna, this study takes into account thirty-four bioactive compounds as the chosen ligands in molecular docking. The binding affinity, inhibition constant (Ki), and the interacting residues of these phytochemicals with the receptors are compared with the docking results of twelve selected standard anticancer drugs. The study finally categorizes the phytochemicals that can potentially act as multitargeted inhibitors of proteins associated with lung cancer. Results: The results from PyRx highlighted the phytoconstituents having a higher binding affinity with inhibition constant comparable to the standard drugs. Among the standard anticancer drugs, alectinib, pralsetinib, and ibrutinib are marked as potent inhibitors of several lung cancer receptors. The phytochemicals of Terminalia arjuna proved to be the potential candidates against ALK2, ALK5, DDR2, BRAF, KRAS, Tankyrase, vasopressin V2, VEGFR1 and VEGFR2 mediated lung cancer but the effectiveness (in comparison to the standard drugs) is limited against Bcl-2, IL22R1, NCAM, RET, MET and ROS1 receptors. Conclusions: The findings indicate that phytochemicals namely luteolin, friedelin, oleanolic acid, and 14,16-dianhydrogitoxigenin bind strongly to multiple receptors under consideration with high affinity and hence could be investigated as effective alternatives for treating lung cancer with minimal side effects.

Novel pyridine bearing pentose moiety-based anticancer agents: design, synthesis, radioiodination and bioassessments

Pyridine compounds are one of the most important heterocyclic derivatives showing wide ranges in biological and pharmacological activities. Green chemistry eliminates or reduces the generation of hazardous compounds. It prevents pollution at a molecular level. The microwave technique used in heterocyclic compound synthesis is also an important branch of green chemistry techniques. In this study, we report designing and synthesizing a new pyridine-bearing pentose moiety via a one-pot multicomponent reaction using D-glucose and also investigate its behavior and reactivity toward some simple and heterocyclic amino derivatives. The chemical structures of the synthesized compounds were characterized and tested for their cytotoxic activities. Some of the test compounds exhibited slight to high cytotoxic activities against Caco2 (colon cancer) cells, HepG2 (hepatocellular carcinoma) cells and MCF-7 (human breast cancer) cells by MTT assay. The results showed clearly that compound 4 and compound 8 displayed strongest to moderate cytotoxic activity against the HepG2, Caco2 and MCF-7 respectively and compound 1 showed good activity against MCF-7 in comparison to the standard anticancer drug doxorubicin. These data were by cytopathological examination. An in-vivo radioactive tracing study of compound 4 proved its targeting ability to sarcoma cells in a tumor-bearing mice model. Our findings suggest that the synthesized compounds may be promising candidates as novel anticancer agents.

Sesamol as a potent anticancer compound: from chemistry to cellular interactions.

Sesamol (SM), a well-known component isolated from sesame seeds (Sesamum indicum), used in traditional medicines in treating numerous ailments. However, numerous molecular investigations revealed the various mechanisms behind its activity, emphasizing its antiproliferative, anti-inflammatory, and apoptosis-inducing properties, preventing cancer cell spread to distant organs. In several cells derived from various malignant tissues, SM-regulated signal transduction pathways and cellular targets have been identified. This review paper comprehensively describes the anticancer properties of SM and SM-viable anticancer drugs. Additionally, the interactions of this natural substance with standard anticancer drugs are examined, and the benefits of using nanotechnology in SM applications are explored. This makes SM a prime example of how ethnopharmacological knowledge can be applied to the development of contemporary drugs.

Ultrasound-activated prodrug-loaded liposome for efficient cancer targeting therapy without chemotherapy-induced side effects.

Off-targeted distribution of chemotherapeutic drugs causes severe side effects, further leading to poor prognosis and patient compliance. Ligand/receptor-mediated targeted drug delivery can improve drug accumulation in the tumor but it always attenuated by protein corona barriers. To address these problems, a radically different strategy is proposed that can leave the off-targeted drugs inactive but activate the tumor-distributed drugs for cancer-targeting therapy in a tumor microenvironment-independent manner. The feasibility and effectiveness of this strategy is demonstrated by developing an ultrasound (US)-activated prodrug-loaded liposome (CPBSN38L) comprising the sonosensitizer chlorin e6 (Ce6)-modified lipids and the prodrug of pinacol boronic ester-conjugated SN38 (PBSN38). Once CPBSN38L is accumulated in the tumor and internalized into the cancer cells, under US irradiation, the sonosensitizer Ce6 rapidly induces extensive production of intracellular reactive oxygen species (ROS), thereby initiating a cascade amplified ROS-responsive activation of PBSN38 to release the active SN38 for inducing cell apoptosis. If some of the injected CPBSN38L is distributed into normal tissues, the inactive PBSN38 exerts no pharmacological activity on normal cells. CPBSN38L exhibited strong anticancer activity in multiple murine tumor models of colon adenocarcinoma and hepatocellular carcinoma with no chemotherapy-induced side effects, compared with the standard first-line anticancer drugs irinotecan and topotecan. This study established a side-effect-evitable, universal, and feasible strategy for cancer-targeting therapy.

Exploring the Potential of Chemical Constituents of Datura metel in Breast Cancer from Molecular Docking Studies

Breast cancer remains a pervasive health challenge worldwide, prompting the exploration of novel therapeutic prospects. Datura metel has long been recognized for its pharmacological properties, particularly in containing various bioactive compounds like alkaloids, flavonoids, and terpenoids. This review focuses on the potential of chemical constituents sourced from Datura metel, a traditional medicinal plant, in combating breast cancer, primarily through molecular docking studies. The review meticulously scrutinizes the chemical composition of Datura metel, emphasizing the identified compounds known for their therapeutic attributes. Through an extensive analysis of molecular docking studies, the interactions between these Datura metel constituents and crucial molecular targets associated with breast cancer are elucidated. The phytoconstituents (compound 1-13) were found to be more potent as compare to Tomoxifen citrate as standard anticancer drug. The findings presented herein beckon for further exploration, highlighting a promising avenue in the pursuit of effective and targeted treatments for breast cancer. In conclusion, this review emphasizes the synergistic integration of computational approaches with traditional knowledge, accelerating the discovery and development of innovative breast cancer therapies.

Identification of hub genes to determine drug-disease correlation in breast carcinomas.

The exact molecular mechanism underlying the heterogeneous drug response against breast carcinoma remains to be fully understood. It is urgently required to identify key genes that are intricately associated with varied clinical response of standard anti-cancer drugs, clinically used to treat breast cancer patients. In the present study, the utility of transcriptomic data of breast cancer patients in discerning the clinical drug response using machine learning-based approaches were evaluated. Here, a computational framework has been developed which can be used to identify key genes that can be linked with clinical drug response and progression of cancer, offering an immense opportunity to predict potential prognostic biomarkers and therapeutic targets. The framework concerned utilizes DeSeq2, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Cytoscape, and machine learning techniques to find these crucial genes. Total RNA extraction and qRT-PCR were performed to quantify relative expression of few hub genes selected from the networks. In our study, we have experimentally checked the expression of few key hub genes like APOA2, DLX5, APOC3, CAMK2B, and PAK6 that were predicted to play an immense role in breast cancer tumorigenesis and progression in response to anti-cancer drug Paclitaxel. However, further experimental validations will be required to get mechanistic insights of these genes in regulating the drug response and cancer progression which will likely to play pivotal role in cancer treatment and precision oncology.

Biotransformation of metenolone acetate and epiandrosterone by fungi and evaluation of resulting metabolites for aromatase inhibition

The present study describes the microbial transformation of anabolic drugs, metenolone acetate (1), and epiandrosterone (6). Three new metabolites, 6β,17β-dihydroxy-1-methyl-3-oxo-5α-androst-1-en (2), 5α,15α-dihydroxy-1-methyl-3-oxo-1-en-17-yl acetate (3), 15β-hydroxy-1-methyl-3-oxo-5α-androst-1,4-dien-17-yl acetate (4), and a known metabolite, 17β-hydroxy-1-methyl-4-androstadiene-3-one (5) were obtained by biotransformation of metenolone acetate (1) via Trametes hirsuta mushroom. Metabolites 7, and 8 were obtained from the incubation of epiandrosterone (6) with Cunninghamella blakesleeana. While bioconversion of compound 6 with Aspergillus alliaceus yielded seven known metabolites 9–15. Modern spectroscopic techniques were employed for the structure elucidation of biotransformed products. All compounds were evaluated for their aromatase inhibitory activity. Among them, new metabolite 3 exhibited a significant human placental aromatase activity with an IC50 = 19.602 ± 0.47 µM, as compared to standard anti-cancer drug exemestane (IC50 = 0.232 ± 0.031 µM), whereas, metabolite 5 (IC50 = 0.0049 ± 0.0032 µM) exhibited a very potent activity. While substrate 6, and metabolites 2, 7, and 9 were found inactive. Aromatase plays a key role in the biosynthesis of estrogen hormone, responsible for cancer cell proliferation. Its inhibition is therefore targeted for the treatment of ER + breast cancer. Further structural modifications (lead optimization) of compound 3 can lead to more potent aromatase inhibition for possible treatment of ER + breast cancer.

Fabrication and evaluation of anticancer potential of diosgenin incorporated chitosan-silver nanoparticles; in vitro, in silico and in vivo studies

The discovery of effective therapeutic approaches with minimum side effects and their tendency to completely eradicate the disease is the main challenge in the history of cancer treatment. Fenugreek (FGK) seeds are a rich source of phytochemicals, especially Diosgenin (DGN), which shows outstanding anticancer activities. In the present study, chitosan-silver nanoparticles (ChAgNPs) containing Diosgenin (DGN-ChAgNPs) were synthesized and evaluated for their anticancer activity against breast cancer cell line (MCF-7). For the physical characterization, the hydrodynamic diameter and zeta potential of DGN-ChAgNPs were determined to be 160.4 ± 12 nm and +37.19 ± 5.02 mV, respectively. Transmission electron microscopy (TEM) showed that nanoparticles shape was mostly round with smooth edges. Moreover, DGN was efficiently entrapped in nanoformulation with good entrapment efficacy (EE) of ~88 ± 4 %. The in vitro anti-proliferative activity of DGN-ChAgNPs was performed by sulforhodamine B (SRB) assay with promising inhibitory concentration of 6.902 ± 2.79 μg/mL. DAPI staining, comet assay and flow cytometry were performed to validate the anticancer potential of DGN-ChAgNPs both qualitatively and quantitatively. The percentage of survival rate and tumor reduction weight was evaluated in vivo in different groups of mice. Cisplatin was used as a standard anticancer drug. The DGN-ChAgNPs (12.5 mg/kg) treated group revealed higher percentage of survival rate and tumor reduction weight as compared to pure DGN treated group. These findings suggest that DGN-ChAgNPs could be developed as potential treatment therapy for breast cancer.

Melittin: a possible regulator of cancer proliferation in preclinical cell culture and animal models.

Melittin is a water-soluble cationic peptide derived from bee venom that has been thoroughly studied for the cure of different cancers. However, the unwanted interactions of melittin produce hemolytic and cytotoxic effects that hinder their therapeutic applications. To overcome the shortcomings, numerous research groups have adopted different approaches, including conjugation with tumor-targeting proteins, gene therapy, and encapsulation in nanoparticles, to reduce the non-specific cytotoxic effects and potentiate their anti-cancerous activity. This article aims to provide mechanistic insights into the chemopreventive activity of melittin and its nanoversion in combination with standard anti-cancer drugs for the treatment of cancer. We looked over the pertinent research on melittin's chemopreventive properties in online databases such as PubMed and Scopus. In the present article, the anti-cancerous effects of melittin on different cancers have been discussed very nicely, as have their possible mechanisms of action to act against different tumors. Besides, it interacts with different signal molecules that regulate the diverse pathways of cancerous cells, such as cell cycle arrest, apoptosis, metastasis, angiogenesis, and inflammation. We also discussed the recent progress in the synergistic combination of melittin with standard anti-cancer drugs and a nano-formulated version of melittin for targeted delivery to improve its anticancer potential.

Isolation of anticancer bioactive secondary metabolites from the sponge-derived endophytic fungi Penicillium sp. and in-silico computational docking approach.

Fungus-derived secondary metabolites are fascinating with biomedical potential and chemical diversity. Mining endophytic fungi for drug candidates is an ongoing process in the field of drug discovery and medicinal chemistry. Endophytic fungal symbionts from terrestrial plants, marine flora, and fauna tend to produce interesting types of secondary metabolites with biomedical importance of anticancer, antiviral, and anti-tuberculosis properties. An organic ethyl acetate extract of Penicillium verruculosum sponge-derived endophytic fungi from Spongia officinalis yielded seven different secondary metabolites which are purified through HPLC. The isolated compounds are of averufin (1), aspergilol-A (2), sulochrin (3), monomethyl sulochrin (4), methyl emodin (5), citreorosein (6), and diorcinol (7). All the seven isolated compounds were characterized by high-resolution NMR spectral studies. All isolated compounds', such as anticancer, antimicrobial, anti-tuberculosis, and antiviral, were subjected to bioactivity screening. Out of seven tested compounds, compound (1) exhibits strong anticancer activity toward myeloid leukemia. HL60 cell lines have an IC50 concentration of 1.00μm, which is nearly significant to that of the standard anticancer drug taxol. A virtual computational molecular docking approach of averufin with HL60 antigens revealed that averufin binds strongly with the protein target alpha, beta-tubulin (1JFF), with a -10.98 binding score. Consecutive OSIRIS and Lipinski ADME pharmacokinetic validation of averufin with HL60 antigens revealed that averufin has good pharmacokinetic properties such as drug score, solubility, and mutagenic nature. Furthermore, aspergilol-A (2) is the first report on the Penicillium verruculosum fungal strain. We concluded that averufin (1) isolated from Penicillium verruculosum can be taken for further preliminary clinical trials like animal model in-vivo studies and pharmacodynamic studies. A future prospect of in-vivo anticancer screening of averufin can be validated through the present experimental findings.

Solution stage fluorescence and anticancer properties of azomethine compounds from sulpha drugs: Synthesis, experimental and theoretical insights

In this comprehensive scientific study, we present the synthesis, characterization, and detailed analysis of two Schiff base compounds, (E)-4-((4-bromobenzylidene)amino)-N-(thiazole-2-yl)benzenesulfonamide (4BRTH) and (E)-4-((1-phenylethylidene)amino)-N-(thiazole-2-yl)benzenesulfonamide (APTH). These Schiff bases were synthesized from sulfathiazole, 4-bromobenzaldehyde, and acetophenone, employing acid-catalyzed reactions. The compounds were characterized using spectroscopic techniques, including UV, IR, and NMR. Notably, the UV spectra revealed absorption peaks at 295, 328, and 345 nm for 4BRTH and 270, 295, and 325 nm for APTH, with calculated oscillator strengths of 0.497, 0.3637, and 0.4138 for 4BRTH and 0.4841, 0.0005, and 0.1247 for APTH. Furthermore, fluorescence studies indicated unique emission peaks at 401 and 706 nm for 4BRTH and 412 and 725 nm for APTH, with excitation wavelengths at 297 nm for 4BRTH and 289 nm for APTH. The compounds displayed fluorescence characteristics, further showcasing their potential as fluorescent probes. Computational simulations were performed using various theoretical levels, including DFT calculations with the B3LYP functional and cc-pVDZ basis sets. The HOMO-LUMO gap was found to be 1.83 eV for 4BRTH and 2.04 eV for APTH, suggesting their reactivity towards other molecules. Theoretical binding energies from molecular docking studies against the breast cancer-related protein 6NLV revealed binding affinities of -18.63 kcal/mol for 4BRTH and -19.84 kcal/mol for APTH, providing insights into their potential anti-cancer activity. Moreover, in vitro anti-cancer assays conducted on MCF7 breast cancer cells demonstrated that both compounds exhibited anti-cancer activity with IC50 values. Importantly, the IC50 values were within the range of the standard anti-cancer drug cisplatin, which had an IC50 value of 62.5 μg/mL. These findings underscore the potential of 4BRTH and APTH as candidates for further anti-cancer drug development.