Cancer PC-3 Cells Research Articles

New 1,2,4-triazole based eugenol derivatives as antiCOX-2 and anticancer agents

Due to chronic inflammation, elevated cyclooxygenase (COX-2) level leads to tumorigenesis, proliferation, invasion, angiogenesis and metastasis. Therefore, suppression of COX-2 enzyme is a fascinating approach in cancer treatment. In the present study, natural product eugenol was modified to develop new 1,2,4-triazole derivatives as antiCOX-2 and antiproliferative agents. The structures of newly prepared derivatives were established using sophisticated analytical techniques. The antiproliferative result showed compound 10 to be equipotent to doxorubicin towards MDA-MB 231 and PC-3 cancer cells with IC50 1.42 and 5.69 μM, respectively and potent COX-2 inhibitor with IC50 0.28 μM. Compound 10 was also non carcinogenic, non mutagenic with good drug likeness property as depicted by in silico physicochemical and pharmacokinetic studies. The docking results against COX-2 protein showed highest binding energy for compound 10 which was found to be in consistent with the cytoxicity and COX-2 results. In conclusion, compound 10 could harness COX-2 and cell proliferation and could be a promising candidate in cancer therapy.

Lysosome-targeting and legumain-triggered 68Ga-labeled probe for enhanced tumor PET imaging

Legumain is overexpressed in diverse tumors, serving as a significant tumor biomarker. Our study aimed to develop a new positron emission tomography (PET) probe [68Ga]Ga-NOTA-SF-AANM for imaging the expression level of legumain in vivo. The radio-labeling of [68Ga]Ga-NOTA-SF-AANM was accomplished within 15 min. The probe has good stability in vitro. NOTA-SF-AANM exhibited rapid response to recombinant human legumain enzyme, enabling intramolecular condensation cyclization. Cellular uptake and lysosomal co-localization experiments demonstrated that the probe was able to differentiate specifically between MDA-MB-468 and PC-3 cancer cells with varying degrees of legumain expression. PET imaging displayed a significant and persistent signal (3.59 ± 0.30 %ID/mL at 60 min) in MDA-MB-468 tumors, while PC-3 tumors exhibited lower radioactivity (1.08 ± 0.35 %ID/mL at 60 min), further validating the specific targeting of [68Ga]Ga-NOTA-SF-AANM towards legumain. [68Ga]Ga-NOTA-SF-AANM is a promising tool for precise diagnosis of legumain-related diseases due to its advantages in radio-labeling and accurate monitoring of legumain expression levels.

Novel N3-Schiff base and its zinc halide/pseudohalide complexes: Antimicrobial, antioxidant, cytotoxicity and burn wound healing activities

A new N3-tridentate Schiff base ligand(L) was synthesized by condensation reaction of 2-methoxycinnamaldehyde and diethylenetriamine. Thereafter some new zinc complexes formulated as [ZnLX2] (X is halide or pseudo-halide) were prepared using this chelating ligand. The suggested structures of these compounds were identified by melting point and molar conductivity measuring, UV–Visible, FT/IR, 1H and 13C NMR and MASS spectral analyses. Moreover, the thermal behaviors of the ligand and zinc complexes were investigated under N2 atmosphere and at a heating rate of 20 °C/min. Zinc bromide and chloride complexes were synthesized in nanostructured sizes by sonochemical method and used as precursor to prepare nanostructured ZnO approved by SEM, EDX and XRD analyzes. Furthermore antibacterial, antifungal and antioxidant properties were evaluated by well diffusion, ferric reducing antioxidant power (FRAP) and 2, 2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) methods respectively. Cytotoxicity properties of the ligand and zinc complexes were assessed against prostate cancerous cell lines (PC3) as compared with HUVEC normal cells. The morphology of PC3 cancer cells treated by the ligand and some zinc complexes were also visualized by images. Eventually, burn wound healing activities of the ligand and zinc chloride complex were examined for healing of the second degree burns in the rats in a period of 20 days.

C-30 analogues of betulinic acid as potent cytotoxic agents: design, synthesis, biological evaluation and in-silico studies

In an endeavour to improve the anti-cancer activity of betulinic acid (BA), a series of C-30 derivatives were envisaged and synthesized with a novel synthetic approach. All the derivatives were evaluated for cytotoxic activity by MTT assay against six different human cancer cell lines: prostate (PC3), lung (A549), human hepatocellular carcinoma (HepG2), human leukemia (Molt-4), pancreatic (Panc-1) and breast (MCF-7). The data revealed that compound 16 was observed most promising cytotoxic agent with IC50 values of 7.43 μM, 9.1 μM, and 9.64 μM against A549, MCF-7, and PC3 cancer cell lines respectively. A further mechanistic study confirmed compound 16 showed significant cell death by arresting the cell cycle in the G1 phase and inducing apoptosis in A549 cells. Communicated by Ramaswamy H. Sarma

Folic Acid-Conjugated Chitosan-Coated Solid Lipid Nanoparticles: Precision Targeting of Artemisia vulgaris Essential Oils for Anticancer Therapy.

In this study, we developed Solid Lipid Nanoparticles (SLN-NPs) loaded with Artemisia vulgaris essential oil and coated with folic acid-chitosan (AVEO-SCF-NPs) to enhance drug delivery in biotechnology and pharmaceutical sectors. AVEO-SCF-NPs were synthesized using homogenization and ultra-sonication methods and comprehensively characterized. These nanoparticles exhibited a particle size of 253.67 nm, Polydispersity Index (PDI) of 0.26, zeta potential (ζ-p) of +39.96 mV, encapsulation efficiency (%EE) of 99.0 %, and folic acid binding efficiency (% FB) of 46.25 %. They effectively inhibited MCF-7, HT-29, and PC-3 cancer cells with IC50 values of 48.87 μg/mL, 88.48 μg/mL, and 121.34 μg/mL, respectively, and demonstrated antibacterial properties against Gram-positive strains. AVEO-SCF-NPs also exhibited scavenging effects on ABTS (IC50 : 203.83 μg/mL) and DPPH (IC50: 680.86 μg/mL) free radicals and inhibited angiogenesis, as confirmed through CAM and qPCR assays. Furthermore, these nanoparticles induced apoptosis, evidenced by up-regulation of caspase 3 and 9, down-regulation of TNF-α genes, and an increase in SubG1 phase cells. The high loading capacity of SCF-NPs for AVEO, coupled with their multifaceted biological properties, highlights AVEO-SCF-NPs as promising candidates for cancer therapy in the biotechnology and pharmaceutical industries.

Novel carbazolyl-thiazolyl-chromone and carbazolyl-thiazolyl-pyrazole hybrids: synthesis, cytotoxicity evaluation and molecular docking studies.

A simple synthetic method was performed to design a novel series of polycyclic systems consisting of carbazole-thiazolidinone-chromone hybrids 4a-e and carbazole-thiazolidinone-pyrazole hybrids 5a-e in excellent yields. The methodology depended on the one-pot four-component reaction of 3-amino-9-ethylcarbazole, substituted isothiocyanates, ethyl bromoacetate and 6-methyl-3-formylchromone in ethanol under ultrasound waves at 50 °C to give the carbazole-thiazolidinone-chromone hybrids 4a-e. The latter isolated products were treated with hydrazine hydrate in ethanol under ultrasound waves at 50 °C affording the corresponding carbazole-thiazolidinone-pyrazole hybrids 5a-e. Spectral and analytical data confirmed the structures of all the synthesized compounds. The target compounds were screened for their in vitro anticancer activities against HCT116, PC3 and HepG2 cancer cell lines using the standard SRB method. Fortunately, both compounds 5dand5e were the most active against all cancer cell lines compared with doxorubicin and can be promising anticancer agents. Both bioactive products 5band5e were studied by the molecular docking to see how they bind with VEGFR-2 receptor. The results indicated that those compounds exhibited high affinities towards VEGFR-2 and established remarkably similar interactions to those of the powerful VEGFR-2-KDR.

Cordia Dichotoma: A Comprehensive Review of its Phytoconstituents and Endophytic Fungal Metabolites and their Potential Anticancer Effects.

Cordia Dichotoma is a valuable medicinal plant belonging to the family Boraginaceae. It consists of several beneficial secondary metabolite components, including alkaloids, carbohydrates, flavonoids, glycosides, saponins, and tannins. Numerous studies have been conducted to assess the anticancer properties of Cordia Dichotoma on MCF-7, A-549, PC3, and HeLa cancer cell lines, primarily utilizing ethanolic extract, methanolic extract, and chloroform extract. The results of these studies have demonstrated significant effects. Furthermore, several studies have revealed the rich phytoconstituent content of Cordia Dichotoma with some significant components previously utilized by researchers to investigate the anticancer properties of specific compounds. This review discusses several of these components, including β-sitosterol, α-amyrin, Quercitrin, Robinin, betulin, Taxifolin, and Hesperetin. Additionally, a recent study uncovered that the anticancer effect of metabolites from endophytic fungi residing on the Cordia Dichotoma plant is attributed to a property of the plant itself. This review focuses on the current state of anticancer research related to this plant and its components.

Brønsted acid- and Ni(II)-catalyzed C-H oxidation/rearrangement of cyclotriveratrylenes (CTVs) to cyclic and acyclic quinones as potential anti-cancer agents.

This paper describes a simple and practical protocol for the direct synthesis of acyclic and cyclic quinone derivatives via an acid-promoted nickel(II)-catalyzed inner rim C-H oxidation of cyclotriveratrylene (CTV) and its analogues. The cyclic quinone derivatives resulted from trimethoxy-cyclotriveratrylene (TCTV) through C-C bond formation via intramolecular ipso substitution followed by subsequent anionic rearrangement containing stereo-vicinal quaternary centers. The DFT calculations strongly support the experimental findings and reveal the role of Brønsted acids in the C-H bond activation of CTV. All the newly synthesized compounds were screened for their in vitro anti-cancer activity using colorimetric SRB assay analysis. Among them, compounds 3a, 3d, 3h, 4a, 4b, 4c and 4e exhibited moderate anticancer activity against A549, HCT-116, PC-3, MDA-MB-231, HEK-293 and SW620 human cancer cell lines.

Semisynthesis and Cytotoxic Activities of Novel Oxime Ester Derivatives of the Diterpene Stemodin

Stemodin (1) is a diterpene produced by Stemodia maritima L. (Scrophulariaceae) and shows antiviral and tumor cell proliferation inhibitory activities. Chemical modifications of 1 were performed to produce the known stemodinone (2), two new stemodinone oximes, Z (3) and E (4), and seven new oxime esters derivatives (5, 6, 7, 8, 9, 10, and 11). All derivatives were evaluated for their cytotoxic activity in HL60 (promyelocytic leukemia), SNB-19 (astrocytoma), HCT-116 (colon carcinoma), and PC3 (prostate) human cancer cell lines, and L929 (healthy murine cells). Oximes 3 and 4 showed lower cytotoxic values than 1 against all cancer cell lines tested. However, esters 9 and 10 exhibited cell growth inhibition percentages higher than 1 against PC3, SNB-19, and HCT-116 cancer cell lines, ranging from 62.96 to 94.27%. Many of these values exceed that presented by doxorubicin (66.05-86.87%). All compounds showed no cytotoxic effect on healthy cells at the tested concentration of 25 µg mL-1.

Anticancer activity of zinc oxide nanoparticles on prostate and colon cancer cell line.

Considering the numerous drug resistance in cancer and the advancement of science in nanomedicines, it was decided to compare the effectiveness of zinc oxide nanoparticles in colon and prostate cell lines. Considering the importance of factors and Oxidative stress pathways in cancer prevention, the aim of the study is based on oxidative stress mechanisms. In order to evaluate the effects of zinc oxide nanoparticles on colon and prostate cell lines, oxidative stress factors ROS, MDA, and GSH and mitochondrial function were evaluated. The data was analyzed with Prism v8 software, and the significance level was considered to be P<0.05. The results showed that nanoparticles induce ROS and reduce intracellular glutathione by destroying and disrupting mitochondrial function, and by increasing ROS production, damage to the lipid membrane and an increase in MDA were also evident. This effect was dose-dependent and the greatest at a concentration of 25μg/mL. Also, ZnO nanoparticles performed better in the HT29 cell line than in the PC3 cell line. This study showed that exposure of HT29 and PC3 cancer cells to zinc oxide nanoparticles at different concentrations inhibited growth by cytotoxic effects.

Design, synthesis, molecular docking and biological evaluation of 1,3,5-trisubstituted-1H-pyrazole derivatives as anticancer agents with cell cycle arrest, ERK and RIPK3- kinase activities

The need for new ERK and RIPK3 kinase modulators arises from their central roles in cellular processes, especially in diseases like cancer. This research focused on a ligand-based strategy, incorporating previously documented 1,3,5-trisubstituted-1H-pyrazole derivatives, to craft innovative inhibitors specifically targeting ERK and RIPK3 kinases. Compounds 6, 7, 10a, 10c, and 10d exhibited significant cytotoxicity against PC-3 and MCF-7 cancer cell lines, with IC50 values ranging from 21.9 to 28.6 µM and 3.90–35.5 µM, respectively values surpassing those of the reference compound Doxorubicin. Additionally, cell cycle analysis revealed intriguing results, particularly with 10d inducing cell cycle arrest at the S phase in treated PC-3 cells, indicating potential DNA replication phase inhibition. Moreover, compounds 6, 10a, and 10d exhibited promising results in the in vitro kinase assay supported by molecular docking studies. The core scaffold of these compounds established interactions with vital amino acids within the active pockets of ERK and RIPK3 kinases, thereby securely anchoring them in place. These findings underscore the development of promising modulators for ERK and RIPK3 kinases, suggesting their potential for future contributions to cancer treatments.

Transferrin-Bearing, Zein-Based Hybrid Lipid Nanoparticles for Drug and Gene Delivery to Prostate Cancer Cells.

Gene therapy holds great promise for treating prostate cancer unresponsive to conventional therapies. However, the lack of delivery systems that can transport therapeutic DNA and drugs while targeting tumors without harming healthy tissues presents a significant challenge. This study aimed to explore the potential of novel hybrid lipid nanoparticles, composed of biocompatible zein and conjugated to the cancer-targeting ligand transferrin. These nanoparticles were designed to entrap the anti-cancer drug docetaxel and carry plasmid DNA, with the objective of improving the delivery of therapeutic payloads to prostate cancer cells, thereby enhancing their anti-proliferative efficacy and gene expression levels. These transferrin-bearing, zein-based hybrid lipid nanoparticles efficiently entrapped docetaxel, leading to increased uptake by PC-3 and LNCaP cancer cells and significantly enhancing anti-proliferative efficacy at docetaxel concentrations exceeding 1 µg/mL. Furthermore, they demonstrated proficient DNA condensation, exceeding 80% at polymer-DNA weight ratios of 1500:1 and 2000:1. This resulted in increased gene expression across all tested cell lines, with the highest transfection levels up to 11-fold higher than those observed with controls, in LNCaP cells. These novel transferrin-bearing, zein-based hybrid lipid nanoparticles therefore exhibit promising potential as drug and gene delivery systems for prostate cancer therapy.

Synthesis and biological evaluation of novel salicylidene uracils: Cytotoxic activity on human cancer cell lines and inhibitory action on enzymatic activity.

A series of salicylidene uracil (1-18) derived from 5-aminouracil and substituted salicylaldehydes were analyzed for cytotoxic activity and enzyme inhibitory potency. Nine out of eighteen derivatives (6-8, 10, 12-15, 18) are novel molecules synthesized for the first time in this work, and other derivatives were previously synthesized by our group. The compounds were characterized by Proton nuclear magnetic resonance, carbon nuclear magnetic resonance, fourier transform infrared spectroscopy, and elemental analysis. All compounds were tested for their in vitro cytotoxicity against PC-3 (human prostate adenocarcinoma), A549 (human alveolar adenocarcinoma), and SHSY-5Y (human neuroblastoma) cancer cell lines and the nontumorigenic HEK293 (human embryonic kidney cells) cell line. The 3,5-di-tert-butylsalicylaldehyde derived compound (8) was toxic to PC-3 human prostate adenocarcinoma cells, showing a promising IC50 value at 7.05 ± 0.76 μM. The present study also aimed to evaluate the inhibitory effects of the compounds against several key enzymes, namely carbonic anhydrase I and II (CA I and CA II), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and glutathione reductase (GR), which are implicated in various global disorders, such as Alzheimer's disease, epilepsy, cancer, malaria, diabetes, and glaucoma. The inhibitory profiles of the tested compounds were assessed by determining their Ki values, which ranged from 2.96 to 9.24 nM for AChE, 3.78 to 12.57 nM for BChE, 8.42 to 25.74 nM for CA I, 7.24 to 19.74 nM for CA II, and 0.541 to 1.124 μM for GR. Molecular docking studies were also performed for all compounds. Most derivatives exhibited much more effective inhibitory action compared with clinically used standards. Thus, our findings indicate that the salicylidene derivatives presented in this study are promising drug candidates that need further evaluation.

Aridanin and oleanane-3- O-β-D-glucoside-2′-acetamide obtained from Tetrapleura tetraptera (Schumach. & Thonn) Taub. (Fabaceae) induces potent apoptotic activity in human prostate cancer cells

Ethnopharmacological relevanceTetrapleura tetraptera (Schumach. and Thonn.) Taub. (Fabaceae) is a tropical plant that is used in Cameroon pharmacopeia for the treatment of many cancers including prostate cancer (PCa), which is a major cause of men's death worldwide. The objective of this study was to evaluate the anticancer properties as well as underlying mechanisms of isolates from T. tetraptera on DU145, PC3 and LNCaP cancer cell lines. Materials and methodsEight (8) compounds were purified from T. tetraptera stem bark extract through silica gel column chromatography (CC) and characterized using spectroscopic techniques (1D and 2D NMR), HRESIMS. Cell growth was assessed by a well-characterized MTT assay, while BrdU and clonogenicity assays provided information on the cell proliferation index. Further, the impact of the compounds on cell cycle progression and cell death were performed through Flow cytometry. Cell adhesion, cell migration and chemotaxis along with some proteins of epithelial-mesenchymal transition (EMT) were assayed. ResultsOut of the eight (1–8) isolates from T. tetraptera only oleanane-3-O-β-D-glucoside-2′-acetamide and aridanin showed potent cell growth arrest with an estimated CC50 of 15, 23, 16 and 17, 26, 16 μg/mL on DU145, PC3 and LNCaP cells, respectively. A 15% (DU145) and 25% (LNCaP) increase in apoptotic cells induced by oleanane-3-O-β-D-glucoside-2′-acetamide and aridanin at 10 μg/mL were noticed. Oleanane-3-O-β-D-glucoside-2′-acetamide and aridanin at 2.5 and 10 μg/mL reduced the number of cells in S-phase and raised cells in G2/M phase. At the same concentrations, they decreased the number of invading DU145 cells and increased the adherence of DU145 cells to fibronectin and collagen matrix at tested concentrations, accompanied by an increase in integrin β-1 (10 μg/mL) and integrin β-4 (2.5 μg/mL) expression. Furthermore, a down-regulation of pcdk1, cdk2, Bcl-2, N-Cad, vimentin and cytokeratine 8–18 was noticed while, p19, p27, p53 pAKT, Bax, caspase-3 and E-Cad were up-regulated. ConclusionsThis study outlines for the first time, the anticancer ability of compounds oleanane-3-O-β-D-glucoside-2′-acetamide (4) and aridanin (6) from Tetrapleura tetraptera and proposes their putative mechanisms of action.

Biological investigations of Aspergillus ficuum via in vivo, in vitro and in silico analyses

Serious human health impacts have been observed worldwide due to several life-threatening diseases such as cancer, candidiasis, hepatic coma, and gastritis etc. Exploration of nature for the treatment of such fatal diseases is an area of immense interest for the scientific community. Based on this idea, the genus Aspergillus was selected to discover its hidden therapeutic potential. The genus Aspergillus is known to possess several biologically active compounds. The current research aimed to assess the biological and pharmacological potency of the extracts of less-studied Aspergillus ficuum (FCBP-DNA-1266) (A. ficuum) employing experimental and bioinformatics approaches. The disc diffusion method was used for the antifungal investigation, and the MTT assay was performed to assess the anticancer effects. Mice were employed as an in vivo model to evaluate the antispasmodic effects. A standard spectrophotometric technique was applied to gauge the urease inhibitory activity. The antifungal studies indicate that both n-hexane and ethyl acetate extracts were significantly active against Candida albicans (C. albicans) with their zone of inhibitions (ZOI) values reported as 19 ± 1.06 mm and 25 ± 0.55 mm, respectively at a dose of 30 µg.mL−1. In vitro cytotoxicity assay against HeLa, fibroblast 3T3, prostate PC3, and breast MCF-7 cancer cell lines was performed. The ethyl acetate extract of A. ficuum was found to be significantly active against MCF-7 with its IC50 value of 43.88 µg.mL−1. However, no substantial effects on the percent cell death of HeLa cancer cell lines were observed. In addition, the A. ficuum extracts also inhibited the urease enzyme compared to standard thiourea. The antispasmodic activity of A. ficuum extract was assessed by an in vivo model and the results demonstrated promising activity at 150 mg.kg−1. Molecular docking results also supported the antifungal, anticancer, and antiurease potency of A. ficuum extract. Overall, the results display promising aspects of A. ficuum extract as a future pharmacological source.

Antioxidant and anticancer activities of peanut (Arachis hypogaea L.) skin ultrasound extract

This study evaluates the effect of ultrasound-assisted extraction on the extractability of polyphenols from peanut skins (PS) and their antioxidant, and anticancer activities. The extraction was performed with solid/solvent ratios of 1:20 and 1:30 (w/v) at ultrasound intensity ranging from 5.8 to 15.4 W/cm2 for different extraction times (10, 20, 30 and 40 min). The highest polyphenol yield was 167.46 mg GAE/g dried PS. The most abundant polyphenols were catechin, syringic acid, and vanillic acid. The PS ultrasound extract (PSUE) increased the oxidative stability of sunflower oil by four times its initial level. PSUE possessed high inhibitory activity against MCF-7, HepG-2, HCT-116, and PC-3 cancer cell lines, with IC50 ranging from 1.85 ± 0.13 to 6.1 ± 0.43 μg/ml. In addition, the cytotoxicity of PSUE was examined on HFB4 human normal melanocytes using the MTT assay. These results suggest that PSUE can be used as a natural antioxidant and anticancer agent.

Synthesis of novel nicotinic acid derivatives of potential antioxidant and anticancer activity.

This study comprises the design and synthesis of novel nicotinic acid-based cytotoxic agents with selective inhibitory efficacy against the vascular endothelial growth factor receptor-2 (VEGFR-2). Screening of novel compounds for cytotoxicity was assessed against 60 human cancer cell lines. The two most active compounds, 5b and 5c, and the reference drugs sorafenib and doxorubicin were investigated against HCT-15, PC-3, and CF-295 cancer cell lines. Compound 5c exhibited the highest cytotoxic potential compared to doxorubicin against the HCT-15 and PC-3 tumor cell lines. Moreover, it exhibited higher cytotoxic potential and selectivity toward the HCT-15 cell panel compared with sorafenib. Compound 5c demonstrated promising VEGFR-2 inhibition (concentration needed to inhibit cell viability by 50%, IC50 = 0.068 μM) and superior VEGFR-2 selectivity over the epidermal growth factor receptor and platelet-derived growth factor receptor-β enzymes. It also reduced the total and phosphorylated VEGFR-2 and induced apoptosis, as evidenced by a 4.3-fold rise in caspase-3 levels. The antioxidant potential of the new compounds was determined via measuring the superoxide dismutase (SOD) levels, among which compound 5c exhibited an SOD level almost comparable to ascorbic acid. These results suggested that compound 5c exhibited dual cytotoxic and antioxidant activities. Docking of 5c into the VEGFR-2 pocket showed a similar binding mode to sorafenib. Moreover, the ADME (absorption, distribution, metabolism, and excretion) profile of 5c outlined drug-likeness. Finally, The density functional theory calculations displayed an increased binding affinity of 5c to the target enzyme.

Diversity, Antimicrobial, Antioxidant, and Anticancer Activity of Culturable Fungal Endophyte Communities in Cordia dichotoma.

Endophytic fungi are a significant source of secondary metabolites, which are chemical compounds with biological activities. The present study emphasizes the first-time isolation and identification of such fungi and their pharmacological activities from the medicinal plant Cordia dichotoma, which is native to Jammu, India. The Shannon Wiener diversity index revealed a wide range of fungal endophytes in root (1.992), stem (1.645), and leaf (1.46) tissues. A total of 19 endophytic fungi belonging to nine different genera were isolated from this plant and the majority belonged to the Ascomycota phylum. ITS rRNA gene sequencing was used to identify the fungal strains and they were submitted in NCBI GenBank. The most potent fungal isolate Cladosporium cladosporioides OP870014 had strong antimicrobial, antioxidant, and anticancer activity against MCF-7, HCT-116, and PC-3 cancer cell lines. The LC-MS and GC-MS analyses of the ethyl acetate extract of C. cladosporioides were examined to identify the bioactive metabolites. The major compounds of the crude extract derived from C. cladosporioides OP870014, according to GC-MS, are spiculisporic acid; dibutyl phthalate; phenylethyl alcohol; cyclohexanone, 2,3,3-trimethyl-2-3-methylbutyl; pyrrolo[1,2-a]pyrazine-1,4-dione,hexahydro-3-(phenylmethyl);2,5-piperazinedione,3,6-bis(2-methylpropyl); and heneicosane which possessed antimicrobial, anticancerous, and antioxidant activities. The findings revealed that C. dichotoma has the capacity to host a wide variety of fungal endophytes and that secondary metabolites from the endophytic fungus may be a source of alternative naturally occurring antimicrobial, antioxidant, and cytotoxic compounds.

A Dual Protective Drug Delivery System Based on Lipid Coated Core-Shell Mesoporous Silica for Efficient Delivery of Cabazitaxel to Prostate Cancer Cells

Abstract Many advancements are happening in drug delivery to develop an excellent nanocarrier to deliver drugs to target sites bypassing clinical barriers, thereby improving cellular uptake. Lipid coating on mesoporous silica nanoparticles (MSNs) has significantly reduced the drawbacks of many MSNs and increased their compatibility. This study reports a dual protective acid stimuli-responsive lipid-coated core-shell mesoporous silica nanoparticle (CSMS) conjugated with cabazitaxel showing better drug release, cell uptake, and cytotoxicity, and suitability in the prostate cancer (PC-3) cell line. Initially, monodispersed CSMS were conjugated with cabazitaxel (CBZ) through a hydrazone linker (CBZ@Hy-CSMS), proving its appropriate use in designing a stimuli-responsive system. In the second part, CBZ-conjugated CSMS was coated with a lipid layer (L-CBZ@Hy-CSMS) by the liposome fusion method. The presented dual protective CSMS system showed a significant increase in drug delivery at pH 5.4 compared to 7.4, with a drastic decrease in premature drug release when exposed to pH 7.4. The lipid-coated CSMS showed excellent biocompatibility and better cellular uptake with enhanced cell cytotoxicity in PC-3 cancer cells as compared to the uncoated CSMS. CSMS with a lipid coating combined with a stimuli-responsive system could improve the therapeutic delivery and treatment difficulties in many other cell lines and diseases.

Synthesis, Antiproliferative Activity and In Silico Studies of Chalcones Derived From 4-(Imidazole-1-yl)Acetophenone

In this study, the synthesis of chalcone compounds (1-11) derived from 4-(imidazol-1-yl)acetophenone and the structure determination of these compounds by various spectroscopic methods were carried out. The anticancer activities of compounds 1-11 were examined against HeLa and PC-3 cancer cells at four different concentrations (100, 50, 25, and 5 µM) using the BrdU ELISA assay. It was determined that all molecules except compounds 1 and 6 in HeLa cancer cells and compounds 2 and 8 against PC-3 cancer cells were more active against HeLa and PC-3 than the standard drug 5-fluorouracil (5-FU). The best activity against PC-3 cancer cells was compound 4 (IC50: 1.39±0.00 µM). In addition, compound 11 (IC50: 1.58±0.01 µM) was found to have the highest activity against HeLa cancer cells. Compound 4 against PC-3 cancer cell and compound 11 against HeLa cancer cell displayed cell selective activity. The ADME properties and drug similarities of the molecules 1-11 using the SwissADME software were investigated. According to these properties, compounds 1-11 were found to obey Lipinski rules.