Tested Cancer Cell Research Articles

Codelivery of satraplatin and aminopyrrolic receptor with Pluronic F127-based polyaniline nanoparticles with NIR induced release for combined chemotherapy

The acquired drug resistance of the platinum-based drug is a main obstacle in cancer therapy. Herein, an aminopyrrolic receptor 1 was synthesized to sensitize satraplatin for overcoming the drug resistance as well as improving tumor targeted ability. Thus, Pluronic F127-based polyaniline nanoparticles were designed to co-deliver satraplatin and aminopyrrolic receptor 1, which could control the drug release with the Near Infrared laser irradiation (808 nm) due to the polyaniline mediated photothermal conversion. Biological evaluation shows prepared nanoparticles (Pt-ARNPs) exhibited more effective cytotoxicity (IC50 = 2.7 μM) against the tested cancer cell lines under laser irradiation, compared with free satraplatin or treatment without Near-infrared radiation. Moreover, Pt-ARNPs showed comparable cytotoxicity against A549 and A549/cis cells, implying that the combination of satraplatin and aminopyrrolic receptor 1 with nano carrier might be a promising strategy to reduce platinum resistance and improve therapeutic effect in cancer therapy.

SNP rs4971059 predisposes to breast carcinogenesis and chemoresistance via TRIM46-mediated HDAC1 degradation.

Identification of the driving force behind malignant transformation holds the promise to combat the relapse and therapeutic resistance of cancer. We report here that the single nucleotide polymorphism (SNP) rs4971059, one of 65 new breast cancer risk loci identified in a recent genome-wide association study (GWAS), functions as an active enhancer of TRIM46 expression. Recreating the G-to-A polymorphic switch caused by the SNP via CRISPR/Cas9-mediated homologous recombination leads to an overt upregulation of TRIM46. We find that TRIM46 is a ubiquitin ligase that targets histone deacetylase HDAC1 for ubiquitination and degradation and that the TRIM46-HDAC1 axis regulates a panel of genes, including ones critically involved in DNA replication and repair. Consequently, TRIM46 promotes breast cancer cell proliferation and chemoresistance invitro and accelerates tumor growth invivo. Moreover, TRIM46 is frequently overexpressed in breast carcinomas, and its expression is correlated with lower HDAC1 expression, higher histological grades, and worse prognosis of the patients. Together, our study links SNP rs4971059 to replication and to breast carcinogenesis and chemoresistance and support thepursuit of TRIM46 as a potential target for breast cancer intervention.

Novel 1,3,4-thiadiazole/oxadiazole-linked honokiol derivatives suppress cancer via inducing PI3K/Akt/mTOR-dependent autophagy

Honokiol is a bioactive biphenolic component derived from Magnoliae officinalis Cortex (known as “Hou Po” in Chinese), a traditional Chinese herbal medicine. A series of novel 1,3,4-thiadiazole/oxadiazole-linked honokiol derivatives were synthesized and tested for anticancer activity against seven human cancer cell lines in this study. Among all derivatives, 8a had the most potent cytotoxic effect on all tested cancer cells, with IC50 values ranging from 1.62 ± 0.19 to 4.61 ± 0.51 µM, which were 10.38–34.36 folds more potent than the parental honokiol (IC50 values of 30.96 ± 1.81–55.67 ± 0.31 µM). On A549, HCT116, and MDA-MB-231 cell lines, 8a demonstrated 5.69-fold, 5.65-fold, and 4.83-fold greater cytotoxicity than cisplatin, respectively. Compound 8a also had higher selectivity (SI values of 8.41–49.38) towards seven cancer cell lines over the normal cell lines than cisplatin (SI values of 1.24–2.52). The analysis of structure–activity relationships (SARs) revealed that honokiol derivatives bearing 1,3,4-thiadiazoles (8a-j) possessed stronger anticancer activity than those containing 1,3,4-oxadiazoles. Further mechanistic investigation indicated that 8a induced cytotoxic autophagy in cancer cells in a time- and dose-independent manner via suppressing the PI3K/Akt/mTOR pathway. Molecular docking suggested that 8a could bind to the PI3Kα active sites. Additionally, 8a inhibited the migration and invasion of A549 and MDA-MB-231 cancer cells.

Design, synthesis, and biological evaluation of novel 6-(pyridin-3-yl) quinazolin-4(3H)-one derivatives as potential anticancer agents via PI3K inhibition

Abnormal activation of the PI3K/Akt pathway is demonstrated in most of human malignant tumors via regulation of proliferation, cell cycle, and apoptosis. Therefore, drug discovery and development of targeting the PI3K/Akt pathway has attracted great interest of researchers in the development of anticancer drugs. In this study, fifteen 6-(pyridin-3-yl) quinazolin-4(3H)-one derivatives were designed and synthesized. Anticancer activities of the synthetic compounds were evaluated and the potential mechanisms were explored. Several compounds showed certain proliferation inhibitory activity against the tested cancer cells including human non-small cell lung cancer (NSCLC) HCC827, human neuroblastoma SH-SY5Y and hepatocellular carcinoma LM3 cells. Among them, compound 7i and 7m showed the best inhibitory activity against all the cancer cell lines and more active against HCC827 cells with IC50 values of 1.12 μM and 1.20 μM, respectively. In addition, 7i and 7m showed lower inhibitory activity against H7702 cells (human normal liver cells) with IC50 values of 8.66 μM and 10.89 μM, respectively, nearly 8-fold lower than that in HCC827 cells. These results suggested that compounds 7i and 7m had certain selectivity to tumor cells, compared to human normal cells. Further biological studies indicated 7i induced G2/M phase arrests and cell apoptosis of HCC827 cells via PI3K/Akt and caspase dependent pathway. Together, these novel 6-(pyridin-3-yl) quinazolin-4(3H)-one derivatives such as compound 7i and 7m might be lead compounds for development of potential anti-cancer drugs.

Nano-formulations of hesperidin and essential oil extracted from sweet orange peel: Chemical Properties and Biological Activities

Essential oils and Flavonoids are widely recognized for their beneficial effects in possessing many biological activities, such as antioxidant, antimicrobial and cytotoxic properties, also using in food additives and in the cosmetic industry. The aim of this work is to produce nanoparticles of hesperidin and essential oil extracted from waste orange peels, and study its biological impact compared to native products (hesperidin and essential oil) as antioxidant, antimicrobial and cytotoxic. Obtained products (nano-formulation) are characterized by zeta potential, electron scanning microscopy, spectrophotometric method and color analysis. The final products (nano-formulation) were examined as antioxidant agent by two assays (DPPH and ABTS analysis). The antioxidant activity of nano hesperidin and essential oil was evaluated and compared with none formulated. Nanoparticles of hesperidin and essential oil have a great potential in DNA damage prevention compared to their respective controls which were examined by DNA damage assay induced by oxidative stress protection analysis. The in vitro cytotoxic activity of nano formulated hesperidin and essential oil, towards (three cancerous cell lines, including: breast (MCF-7), colorectal (HCT-116) and liver (HepG2), and two non-cancerous control cell lines (fibroblast BJ-1and MCF-12F) compared with native product (essential oil and hesperidin) were examined using MTT assay. The hesperidin and essential oil NPs showed a positive effect on the inhibition of the proliferation of all tested cancer cell line. The antimicrobial activity of hesperidin, essential oil and their nano formulation form was evaluated using well diffusion assay. The nano formulation form of hesperidin and essential oil showed to improve the antimicrobial activity. These findings showed that nano-hesperidin and nano - essential oils play an important role as antioxidant, antimicrobial and cytotoxic agent's effects. These effects might be used for clinical trials and can represent driving formulation for novel chemotherapeutic agents and in food industry. Further studies about the therapeutic effects of nano-hesperidin and essential oil extracted from Egyptian orange peel are requested

A new flavonoid glycoside from Tapinanthus sp. (Loranthaceae) and evaluation of anticancer activity of extract and some isolated compounds

The present work describes the isolation and anticancer activity of Tapinanthus sp. which is a hemi parasitic plant harvested on Combretum glutinosum, the host plant. Phytochemical study afforded a new flavonoid glycoside, tapinantoside (1) isolated for the first time from natural source, alongside six known compounds (2-7). Structure of compounds were elucidated by extensive spectroscopic analyses including 1 D and 2 D NMR, mass spectrometry and by comparison with literature data. The anticancer activity of extract and some isolated compounds were evaluated on glioblastoma (U87MG, C6) and prostate (PC-3) cancer cells. The methanol leaves extract showed good anticancer activity against U87 (IC50 = 21.40 µg/mL) and PC-3 cells (IC50 = 10.26 µg/mL). Compound 3 powerfully inhibits the proliferation of C6 (IC50 = 38.84 µM) and PC-3 cells (IC50 = 21.33 µM), while its effect was moderated on U87MG cells. Compound 1 and 7 were not active on all tested cancer cell lines.

Low-dimensional compounds containing bioactive ligands. Part XVI: Halogenated derivatives of 8-quinolinol N-oxides and their copper(II) complexes

Four N-oxides, 8-quinolinol N-oxide (8-HQNO), 5,7-dichloro-8-quinolinol N-oxide (HdClQNO), 5,7-dibromo-8-quinolinol N-oxide (HdBrQNO) and 7-iodo-8-quinolinol N-oxide (HIQNO) as well as their six copper complexes, CuCl2(8-HQNO)2(H2O) (1), CuCl2(HdClQNO)2(H2O)2 (2), Cu(dClQNO)2(CHCl3) (3), Cu(dClQNO)2(H2O) (4), {[Cu(dBrQNO)2]•2H2O}n (5) and CuCl2(HIQNO)2(H2O)4 (6) were synthesised as possible anticancer agents. Crystal structures of N-oxides contain planar molecules held together via hydrogen bonds involving oxygen atoms of N-oxide groups as acceptors. Crystal structure of 5 represents the first structure of a copper(II) complex with an N-oxide ligand derived from 8-HQNO and is formed by infinite chains. In the chain, the Cu(II) atom coordinates to six oxygen atoms from two bidentate chelating dBrQNO ligands occupying apexes of elongated tetragonal bipyramid with bridging oxygen atoms of N-oxide groups in axial positions. Antiproliferative activity of prepared N-oxides as well as their complexes was studied using in vitro MTT assay against the MDA-MB-231, HCT-116 and A549 cancer cell lines and their selectivity was verified on MSCs cells. Among the tested cancer cell lines, A549 and MDA-MB-231 cells were the most sensitive to the tested complexes. Complex 1 showed the highest cytotoxicity against both tumor cell lines. At concentration, which could be tested in animal models, 1 induced cell death in more than 50% of cancer cells and in 20% of MSCs indicating its selectivity.

Synergistic Effect Induced by Gold Nanoparticles with Polyphenols Shell during Thermal Therapy: Macrophage Inflammatory Response and Cancer Cell Death Assessment.

Simple SummaryPolyphenols are present in a broad variety of plants, and they are known to possess anti-inflammation and anticancer properties. We used extracts from Laurus nobilis to synthetize gold nanoparticles (Au NPs), on which polyphenols were absorbed to form a stable shell (Au NPs@polyphenols). Then, the macrophage inflammation response was assessed, with the aim of using the Au NPs@polyphenols as synergistic tools in the thermal treatment of cancer cell models. We showed that the thermal conductivity enhancement, induced by Au during thermal treatment, increased the anticancer effects of polyphenols. After demonstrating the effectiveness of this system in in vitro cancer cell models, the future challenge will be the in vivo application of Au NPs@polyphenols.Background: In recent decades, gold nanoparticle (Au NP)-based cancer therapy has been heavily debated. The physico-chemical properties of AuNPs can be exploited in photothermal therapy, making them a powerful tool for selectively killing cancer cells. However, the synthetic side products and capping agents often induce a strong activation of the inflammatory pathways of macrophages, thus limiting their further applications in vivo. Methods: Here, we described a green method to obtain stable polyphenol-capped AuNPs (Au NPs@polyphenols), as polyphenols are known for their anti-inflammatory and anticancer properties. These NPs were used in human macrophages to test key inflammation-related markers, such as NF-κB, TNF-α, and interleukins-6 and 8. The results were compared with similar NPs obtained by a traditional chemical route (without the polyphenol coating), proving the potential of Au NPs@polyphenols to strongly promote the shutdown of inflammation. This was useful in developing them for use as heat-synergized tools in the thermal treatment of two types of cancer cells, namely, breast cancer (MCF-7) and neuroblastoma (SH-SY5Y) cells. The cell viability, calcium release, oxidative stress, HSP-70 expression, mitochondrial, and DNA damage, as well as cytoskeleton alteration, were evaluated. Results: Our results clearly demonstrate that the combined strategy markedly exerts anticancer effects against the tested cancer cell, while neither of the single treatments (only heat or only NPs) induced significant changes. Conclusions: Au NP@polyphenols may be powerful agents in cancer treatment.

Synthesis and biological evaluation of platensic alcohol as an adamantane surrogate in antitumor drug lead adaphostin

Adamantane has been widely used as a “lipophilic bullet” in drug discovery and development, due to its unique diamond-like architecture with benign pharmacological/ pharmaceutical properties. Platensimycin is a natural product isolated from a soil streptomycete, which contains an adamantane-like moiety extensively modified from a diterpenoid precursor. In the current study, platensic alcohol was semisynthesized from platensimycin and used as an adamantane surrogate in anticancer drug lead adaphostin. The resulting hybrid platensic alcohol/adaphostin compounds, eg. 4a and 4b, exhibited similar cytotoxic activity with adaphostin against the tested cancer cell lines. In particular, 4b generates significantly more reactive oxygen species (ROS) and shows stronger synergy with the clinically used histone deacetylase inhibitor vorinostat than adaphostin, probably due to the presence of two hydroquinone groups. Density functional theory calculation supports that there could be certain π-π stacking interaction in 4b in aqueous solution, which might explain that 4b has similar serum stability with adaphostin. Our study not only leads to the identification of 4b as a potent ROS generating agent, but showcases a simple scaffold hopping strategy to harvest lipophilic scaffolds from natural products.

The Chemical Composition and Biological Activities of Essential Oils from Zanthoxylum rhetsa Grown in Son La, Northwest Vietnam

Essential oils (EOs) from the stem barks, leaf petioles, fruit petioles, fresh leaves, and fresh and dried fruits of Zanthoxylum rhetsa were extracted by hydrodistillation. The volatile compounds of the products were analyzed by gas chromatography (GC-FID) and gas chromatography/mass spectrometry (GC/MSD). Monoterpene hydrocarbons formed the predominant fraction of all six EO samples, of which sabinene is one of the major components (from 12.37% to 41.13%). For the leaf petiole EO, limonene (25.01%), sabinene (14.56%), and linalool (12.63%) are the major constituents, while the main constituents of fruit petiole EO were terpinolene (19.66%), terpinen-4-ol (19.07%), and sabinene (17.83%). The major components of stem bark EO are terpinen-4-ol (18.23%), sabinene (12.37%), α-phellandrene (7.34%), β-phellandrene (6.32%), and γ-terpinene (6.12%), while sabinene (38.35%), terpinen-4-ol (13.71%), γ-terpinene (6.47%), and limonene (6.02%) are the major constituents of fresh leaf EO. For the EOs of dried fruits and fresh fruits, sabinene, terpinolene, limonene, and terpinen-4-ol are the major constituents. The essential oils were also tested for their cytotoxic and antimicrobial activities. The results revealed that six EOs at concentrations of 50 μg/mL exhibited inhibitory activity against at least one tested cancer cell line but were nontoxic on Vero normal cells. Most EOs showed moderate antimicrobial activity against F. oxysporum; however, there were no obvious activity against B. subtilis and S. aureus.

Dinuclear orthometallated gold(I)-gold(III) anticancer complexes with potent in vivo activity through an ROS-dependent mechanism.

Increasingly explored over the last decade, gold complexes have shown great promise in the field of cancer therapeutics. A major obstacle to their clinical progression has been their lack of in vivo stability, particularly for gold(III) complexes, which often undergo a facile reduction in the presence of biomolecules such as glutathione. Herein, we report a new class of promising anticancer gold(I)-gold(III) complexes with the general formula [XAuI(μ-2-C6F4PPh2)(κ2-2-C6F4PPh2)AuIIIX] [X=Cl (1), Br (2), NO3 (3)] which feature two gold atoms in different oxidation states (I and III) in a single molecule. Interestingly, gold(I)-gold(III) complexes (1-3) are stable against glutathione reduction under physiological-like conditions. In addition, complexes 1-3 exhibit significant cytotoxicity (276-fold greater than cisplatin) toward the tested cancer cells compared to the noncancerous cells. Moreover, the gold(I)-gold(III) complexes do not interact with DNA-like cisplatin but target cellular thioredoxin reductase, an enzyme linked to the development of cisplatin drug resistance. Complexes 1-3 also showed potential to inhibit cancer and endothelial cell migration, as well as tube formation during angiogenesis. In vivo studies in a murine HeLa xenograft model further showed the gold compounds may inhibit tumor growth on par clinically used cisplatin, supporting the significant potential this new compound class has for further development as cancer therapeutic.

Antimicrobial Properties, Cytotoxic Effects, and Fatty Acids Composition of Vegetable Oils from Purslane, Linseed, Luffa, and Pumpkin Seeds

In the present study, the antimicrobial and cytotoxic activities, as well as the fatty acids composition in vegetable seed oils from linseed, purslane, luffa, and pumpkin were evaluated. For this purpose, two linseed oils and one luffa oil were commercially obtained, while purslane and pumpkin oils were obtained from own cultivated seeds. The results showed a variable fatty acids composition among the tested oils, with α-linolenic, linoleic, oleic, palmitic, and stearic acid being the most abundant compounds. In regards to particular oils, linseed oils were a rich source of α-linolenic acid, luffa and pumpkin oil were abundant in linoleic acid, while purslane oil presented a balanced composition with an almost similar amount of both fatty acids. Luffa oil was the most effective against two of the tested cancer cell lines, namely HeLa (cervical carcinoma) and NCI-H460 (non-small cell lung cancer), while it also showed moderate toxicity against non-tumor cells (PLP2 cell line). Regarding the antibacterial activity, linseed oil 3 and pumpkin oil showed the highest activity against most of the tested bacteria (especially against Enterobacter cloacae and Escherichia coli) with MIC and MBC values similar to the used positive controls (E211 and E224). All the tested oils showed significant antifungal activities, especially luffa and pumpkin oil, and for most of the tested fungi they were more effective than the positive controls, as for example in the case of Aspergillus versicolor, A. niger, and Penicillium verrucosum var. cyclopium. In conclusion, the results of our study showed promising antimicrobial and cytotoxic properties for the studied seed oils which could be partly attributed to their fatty acids composition, especially the long-chain ones with 12–18 carbons.

Benzylated Dihydroflavones and Isoquinoline-Derived Alkaloids from the Bark of Diclinanona calycina (Annonaceae) and Their Cytotoxicities.

Diclinanona calycina R. E. Fries popularly known as “envira”, is a species of the Annonaceae family endemic to Brazil. In our ongoing search for bioactive compounds from Annonaceae Amazon plants, the bark of D. calycina was investigated by classical chromatography techniques that yielded thirteen compounds (alkaloids and flavonoids) described for the first time in D. calycina as well as in the genus Diclinanona. The structure of these isolated compounds were established by extensive analysis using 1D/2D-NMR spectroscopy in combination with MS. The isolated alkaloids were identified as belonging to the subclasses: simple isoquinoline, thalifoline (1); aporphine, anonaine (2); oxoaporphine, liriodenine (3); benzyltetrahydroisoquinolines, (S)-(+)-reticuline (4); dehydro-oxonorreticuline (3,4-dihydro-7-hydroxy-6-methoxy-1-isoquinolinyl)(3-hydroxy-4-methoxyphenyl)-methanone) (5); (+)-1S,2R-reticuline Nβ-oxide (6); and (+)-1S,2S-reticuline Nα-oxide (7); tetrahydroprotoberberine, coreximine (8); and pavine, bisnorargemonine (9). While the flavonoids belong to the benzylated dihydroflavones, isochamanetin (10), dichamanetin (11), and a mixture of uvarinol (12) and isouvarinol (13). Compound 5 is described for the first time in the literature as a natural product. The cytotoxic activity of the main isolated compounds was evaluated against cancer and non-cancerous cell lines. Among the tested compounds, the most promising results were found for the benzylated dihydroflavones dichamanetin (10), and the mixture of uvarinol (12) and isouvarinol (13), which presented moderate cytotoxic activity against the tested cancer cell lines (<20.0 µg·mL−1) and low cytotoxicity against the non-cancerous cell line MRC-5 (>25.0 µg·mL−1). Dichamanetin (11) showed cytotoxic activity against HL-60 and HCT116 with IC50 values of 15.78 µg·mL−1 (33.70 µmol·L−1) and 18.99 µg·mL−1 (40.56 µmol·L−1), respectively while the mixture of uvarinol (12) and isouvarinol (13) demonstrated cytotoxic activity against HL-60, with an IC50 value of 9.74 µg·mL−1, and HCT116, with an IC50 value of 17.31 µg·mL−1. These cytotoxic activities can be attributed to the presence of one or more hydroxybenzyl groups present in these molecules as well as the position in which these groups are linked. The cytotoxic activities of reticuline, anonaine and liriodenine have been previously established, with liriodenine being the most potent compound.

Anticancer Effect of Enterocin A-Colicin E1 Fusion Peptide on the Gastric Cancer Cell.

Cancer is one of the most causes of death all over the world, although improvements in its treatment and recognition. Due to the limitations of common anticancer methods, including surgery, chemotherapy, and radiotherapy, attention has been drawn to other anti-cancer compounds, especially natural peptides such as bacteriocins. In this study, we used a combination of two bacteriocins, colicin E1 and enterocin A, against AGS gastric cancer cell lines. In order to evaluate anticancer properties of fusion peptide, we applied MTT assay, real-time PCR, and flow cytometry tests. This is the first report to show the cell growth inhibitory activity of the enterocin A in combination with colicin E1 against AGS human cancer cells. The results of this study showed that this fusion peptide at a concentration of 60.4 µg/mL and 24 h was able to kill half of the tested cancer cells, and treatment of the cells with this concentration increased the expression of bax and caspase 3 genes and reduced the expression of bacl-2 in 24 h. Flow cytometry analysis of annexin V-FITC/propidium iodide results also showed that our peptide was able to induce apoptosis in treated cells compared with control. Taken together, enterocin A-colicin E1 (ent A-col E1) can be considered as a good candidate for anticancer therapies.

In vitro antiproliferative activity of some fluoro-substituted benzimidazole-based scaffolds

In the present work, a series of fluoro-substituted benzimidazole derivatives were designed and synthesized as antiproliferative agents. The antiproliferative activity of these compounds was investigated using MTT assay. Fluoro-substituted benzimidazole derivatives showed significant antiproliferative activity against all the tested cancer cell lines. All the derivatives were found to be less toxic as compared to methotrexate (positive control) in human cells, indicating selective and efficient antiproliferative activity of these benzimidazole derivatives. These findings suggest that compounds ORT14 and ORT15 among this series are most effective and have potential for detailed investigations.

Inhibition effect of oxyepiberberine isolated from Coptis chinensis franch. On non-small cell lung cancer based on a network pharmacology approach and experimental validation

Ethnopharmacological relevanceAs an important Chinese herb, Coptis chinensis Franch. (Huanglian, HL) has a long history of usage for clearing heat, eliminating dampness, purging fire and detoxification in Traditional Chinese Medicine (TCM). HL, also called goldthread, was frequently used for the treatment of typhoid, tuberculosis, epidemic cerebrospinal meningitis, pertussis, and other lung-related diseases. Modern research has shown that HL and its main compounds also have anti-tumor effects. However, studies have not reported whether its main compounds inhibit Non-small cell lung cancer (NSCLC) development and progression. ObjectiveThis study aimed to find out the potential targets and mechanisms of Oxyepiberberine (OPB) isolated from HL in the treatment of NSCLC, using network pharmacology and biological experimental. MethodsSilica gel chromatography column was used to isolate OPB from HL, and the structure of OPB was elucidated using different spectroscopic analysis methods, including 1H-nuclear magnetic resonance (NMR), 13C-NMR and electrospray ionization mass spectrometry (ESI/MS). MTT assay was performed to determine cell proliferation of OPB on A549, H1975 and BEAS-2B cells. Then, the potential targets, pathways and hub genes of OPB for treating NSCLC were screened out through network pharmacology. Based on the results of network pharmacology, core targets of OPB for treating NSCLC were docking with OPB via molecular docking. Wound healing, plate clone, Hoechst staining, and western blot assay were used to verify the function of OPB in treatment of NSCLC. ResultsOPB was isolated from the HL, its molecular formula was identified as C20H17NO5. Through MTT, OPB significantly inhibited the proliferation of H1975 cells and A549 cells, and A549 was chosen as the test cancer cell. Through network pharmacology, 22 potential targets, 156 related-pathways, and 6 hub genes were screened out. The results of molecular docking showed that SRC, BRAF, and MMP9 were the core targets of OPB against NSCLC. Through biological experimental, it was found that OPB inhibited growth and migration of A549 cells. In addition, OPB induced apoptosis in A549 cells. Through western blot assay, the expressions of Src, ERK1/2 and other four proteins were down-regulated, which suggested that OPB inhibited the proliferation of lung cancer cells by down-regulating SRC-FAK-RAS-RAF-MEK-ERK pathway, so as to achieve the anti-NSCLC effect. ConclusionOur study demonstrated that anti-NSCLC effect of OPB through network and experiments, which provided a theoretical basis for the clinical antitumor of OPB, and provided a foundation for further study of OPB.

Discovery of a novel series of substituted quinolines acting as anticancer agents and selective EGFR blocker: Molecular docking study

A Ta2O5-anchored-piperidine-4-carboxylic acid (PPCA) nanoparticle has been synthesized and characterized. It was then used as a highly effective nanocatalyst for the synthesis of quinolin-2(1H)-one derivatives through CO bond functionalization. The special advantage of this heterogeneous solid catalyst is the reusability of the catalyst for up to five cycles without any noticeable reduction in product yields. In comparison, healthy reaction profiles, wide substrate scope, excellent yields and easy workup conditions are the notable highlights of this approach. All the compounds were tested for their anticancer activity against MCF-7 (human breast), HepG2 (human liver), HCT116 (human colorectal), and PC-3 (human prostate) cancer cell lines with the MTT assay. All the compounds were shown to have moderate to good inhibitory effects on tested cancer cell lines. Besides, compounds 5b, 5c and 5d showed good selectivity against epidermal growth factor receptor-tyrosine kinase (EGFR-TK). Molecular docking results showed that active compounds showed a good affinity towards EGFR kinase (PDB ID: 6V6O) by forming two hydrogen bonds with Cys-797 and Tyr-801. All the compounds were screened for computational ADMET and Lipinski analysis.

Effect of light exposure on secondary metabolites production of an endophytic fungus Arthrinium rasikravindrae and its antioxidant and anticancer activities

Abstract. Eltivitasari A, Rahmawati, Gemantari BM, Romadhonsyah F, Nurrochmad A, Wahyuono S, Astuti P. 2021. Effect of light exposure on secondary metabolites production of an endophytic fungus Arthrinium rasikravindrae and its antioxidant and anticancer activities. Biodiversitas 22: 3156-3163. Endophytic microorganisms are one of the promising sources in producing bioactive compounds, to be developed for new drug candidates. They are found to have the ability to generate the same compounds as their host plant. Metabolite producing capacity of the endophytes is known to be affected by light exposure during fermentation process. This study focused on an endophytic fungus Arthrinium rasikravindrae isolated from Coleus amboinicus stem to reveal out its metabolite profiles due to light exposure as well as its bioactivity consequences. A. rasikravindrae was cultured on potato dextrose broth medium for 14 days and fermented in dark and exposed to natural light. Metabolite profiling was performed using TLC and GC-MS analysis. The activities were observed using DPPH assay for antioxidant and MTT assay for cytotoxicity potential. The results showed that A. rasikravindrae ethyl acetate extract produced during dark and exposed to light fermentation conditions contained different compounds but there was some which showed similarity with their host plant. Methyl octadec-9-enoate was found in all fermentation conditions as well as in C. amboinicus stem extract. Besides methyl octadec-9-enoate, methyl palmitate was also found present in both A. rasikravindrae extract fermented exposed to light and its host plant. The antioxidant activity of extract generated from dark fermentation condition was better as compared to that exposed to light with IC50 value of 66.36±0.53 vs 556.92±34.37 µg/mL. However, cytotoxic activity screening against several cancer cell lines exhibited opposing results in which extract from light-exposed fermentation resulted in better cytotoxic activity (IC50 value of 291.40 ± 2.34 µg/mL on WiDr, 336.80 ± 5.05 µg/mL on T47D, and 404.73 ± 3.46 µg/mL on Hela cell lines). Extract obtained from dark fermentation condition showed IC50 value of more than 500 µg/mL in all tested cancer cell lines. Preliminary examination on cytotoxic activity against WiDR cells suggested that the extract from light-exposed fermentation might induce cell death through mechanisms involving cell cycle arrest.

Nitrofurazone repurposing towards design and synthesis of novel apoptotic-dependent anticancer and antimicrobial agents: Biological evaluation, kinetic studies and molecular modeling

Drug repurposing has gained much attention as a cost-effective strategy that plays an exquisite role in identifying undescribed biological activities in clinical drugs. In the present work, we report the repurposing of the antibacterial drug nitrofurazone (NFZ) as a potential anticancer agent against CaCo-2, MDA-MB 231 and HepG-2 cancer cell lines. Novel series of nitrofurazone analogs were then designed considering the important pharmacologic features present in NFZ. Synthesis and biological evaluation of the target compounds revealed their promising anticancer activities endowed with antimicrobial potential and possessing better lipophilicity than NFZ. Compound 7, exclusively, inhibited the growth of all tested cancer cells more potently than NFZ with the least cytotoxicity against normal cells, displaying anti Gram-positive bacterial activities and antifungal potential. Analysis of the stereo-electronic properties of compound 7 via investigating the energies of HOMO, LUMO, HOMO-LUMO energy gap and MEP maps demonstrated its high reactivity and the expected molecular mechanism of action through reduction of the 5-nitrofuryl moiety. Data of the bioactivity studies indicated that the potent anticancer activity of 7 is mainly through increasing intracellular ROS levels and induction of apoptosis via significantly down-regulating the expression of Bcl-2 while up-regulating BAX, p53 and caspase 3 expression levels. Compound 7 potently inhibited the cellular expression levels of antioxidant enzymes GPx1 and GR compared to NFZ. Antioxidant enzymes kinetic studies and blind molecular docking simulations disclosed the mechanistic and structural aspects of the interaction between 7 and both GR and GPx1. Thus, the successful discovery of 7 as a potential dual anticancer-antimicrobial nitrofurazone analog might validate the applicability of drug repurposing strategy in unravelling the unrecognized bioactivity of the present conventional drugs, besides furnishing the way towards more optimization and development studies.

Synthesis, Cytotoxicity, Antioxidant and Antimicrobial Activity of Indole Based Novel Small Molecules

Aim: In this study experiments were carried out to explore antioxidant, antimicrobial, cytotoxic properties of novel indole derivative 1-ethyl-2-phenyl-3-phenylethyl-3-thiophen-2-yl-1Hindole (EPI) together with its effect on glutathione S-transferases (GST) activities in human liver carcinoma (HepG2) cells. Background:: Indoles probably represent one of the most important heterocyclic structures that have been attracting the interest of many scientists in drug discovery. Objective: The present study was carried out to explore antioxidant, antimicrobial, cytotoxic properties of novel indole derivative 1-ethyl-2-phenyl-3-phenylethyl-3-thiophen-2-yl-1H-indole (EPI) and its effect on glutathione S-transferases (GST) activities in human liver carcinoma (HepG2) cells. Materials and Methods: Pd-catalyst Sonogashira coupling reactions, MTT Assay, Antioxidant capacity test, Antimicrobial test, GST enzyme activity test. Results: 1-ethyl-2-phenyl-3-(phenylethynyl)-1H-indole had antioxidant and antimicrobial properties. It displayed significant induction in glutathione S-transferases (GST) enzyme activity in human liver cancer cell lines (HepG2), but cytotoxic effect on all tested cancer cell lines could not be observed. Conclusion:: All of these results showed that 1-ethyl-2-phenyl-3-(phenylethynyl)-1H-indole had antioxidant and antimicrobial properties without cytotoxic effect, which could make it a promising active component with further studies.