NMR Profiling of Ononis diffusa Identifies Cytotoxic Compounds against Cetuximab-Resistant Colon Cancer Cell Lines

In the search of new natural products to be explored as possible anticancer drugs, two plant species, namely Ononis diffusa and Ononis variegata, were screened against colorectal cancer cell lines. The cytotoxic activity of the crude extracts was tested on a panel of colon cancer cell models including cetuximab-sensitive (Caco-2, GEO, SW48), intrinsic (HT-29 and HCT-116), and acquired (GEO-CR, SW48-CR) cetuximab-resistant cell lines. Ononis diffusa showed remarkable cytotoxic activity, especially on the cetuximab-resistant cell lines. The active extract composition was determined by NMR analysis. Given its complexity, a partial purification was then carried out. The fractions obtained were again tested for their biological activity and their metabolite content was determined by 1D and 2D NMR analysis. The study led to the identification of a fraction enriched in oxylipins that showed a 92% growth inhibition of the HT-29 cell line at a concentration of 50 µg/mL.     

Anticancer properties and phenolic contents of sequentially prepared extracts from different parts of selected medicinal plants indigenous to Malaysia

Different parts of four edible medicinal plants (Casearia capitellata, Baccaurea motleyana, Phyllanthus pulcher and Strobilanthus crispus), indigenous to Malaysia, were extracted in different solvents, sequentially. The obtained 28 extracts were evaluated for their in vitro anticancer properties, using the MTS assay, on four human cancer cell lines: colon (HT-29), breast (MCF-7), prostate (DU-145) and lung (H460) cancers. The best anticancer activity was observed for the ethyl acetate (EA) extract of Casearia capitellata leaves on MCF-7 cell lines with IC?? 2.0 μg/mL and its methanolic (MeOH) extract showed an outstanding activity against lung cancer cell lines. Dichloromethane (DCM) extract of Phyllanthus pulcher aerial parts showed the highest anticancer activity against DU-145 cell lines, while significant activity was exhibited by DCM extract of Phyllanthus pulcher roots on colon cancer cell lines with IC50 value of 8.1 μg/mL. Total phenolic content (TPC) ranged over 1-40 mg gallic acid equivalents (GAE)/g. For all the samples, highest yields of phenolics were obtained for MeOH extracts. Among all the extracts analyzed, the MeOH extracts of Strobilanthus crispus leaves exhibited the highest TPC than other samples (p < 0.05). This study shows that the nature of phenol determines its anticaner activity and not the number of phenols present.     

Synthesis and evaluation of antiproliferative activity of substituted N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamides

Several novel N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamide derivatives were prepared as potential antiproliferative agents. The in vitro antiproliferative activity of the synthesized compounds was investigated against a panel of tumor cell lines including breast cancer cell lines (MDA-MB-231, T-47D) and neuroblastoma cell line (SK-N-MC) using MTT colorimetric assay. Etoposide, a well-known anticancer drug, was used as a positive standard drug. Among synthesized compounds, 4-methoxy-N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamide (5i) showed the highest antiproliferative activity against MDA-MB-231, T-47D, and SK-N-MC cells. Furthermore, pentafluoro derivatives 5a and 6a exhibited higher antiproliferative activity than doxorubicin against human leukemia cell line (CCRF-CEM) and breast adenocarcinoma (MDA-MB-468) cells. Structure–activity relationship studies revealed that xanthone benzenesulfonamide hybrid compounds can be used for the development of new lead anticancer agents.     

Ethiopian Medicinal Plants Traditionally Used for the Treatment of Cancer; Part 3: Selective Cytotoxic Activity of 22 Plants against Human Cancer Cell Lines

Medicinal plants have been traditionally used to treat cancer in Ethiopia. However, very few studies have reported the in vitro anticancer activities of medicinal plants that are collected from different agro-ecological zones of Ethiopia. Hence, the main aim of this study was to screen the cytotoxic activities of 80% methanol extracts of 22 plants against human peripheral blood mononuclear cells (PBMCs), as well as human breast (MCF-7), lung (A427), bladder (RT-4), and cervical (SiSo) cancer cell lines. Active extracts were further screened against human large cell lung carcinoma (LCLC-103H), pancreatic cancer (DAN-G), ovarian cancer (A2780), and squamous cell carcinoma of the esophagus (KYSE-70) by using the crystal violet cell proliferation assay, while the vitality of the acute myeloid leukemia (HL-60) and histiocytic lymphoma (U-937) cell lines was monitored in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) microtiter assay. Euphorbia schimperiana, Acokanthera schimperi, Kniphofia foliosa, and Kalanchoe petitiana exhibited potent antiproliferative activity against A427, RT-4, MCF-7, and SiSo cell lines, with IC₅₀ values ranging from 1.85 ± 0.44 to 17.8 ± 2.31 µg/mL. Furthermore, these four extracts also showed potent antiproliferative activities against LCLC-103H, DAN-G, A2780, KYSE-70, HL-60, and U-937 cell lines, with IC₅₀ values ranging from 0.086 to 27.06 ± 10.8 µg/mL. Hence, further studies focusing on bio-assay-guided isolation and structural elucidation of active cytotoxic compounds from these plants are warranted.     

α‐Aminoxy Oligopeptides: Synthesis,Secondary Structure,and Cytotoxicity of a New Class of Anticancer Foldamers

α‐Aminoxy peptides are peptidomimetic foldamers with high proteolytic and conformational stability. To gain an improved synthetic access to α‐aminoxy oligopeptides we used a straightforward combination of solution‐ and solid‐phase‐supported methods and obtained oligomers that showed a remarkable anticancer activity against a panel of cancer cell lines. We solved the first X‐ray crystal structure of an α‐aminoxy peptide with multiple turns around the helical axis. The crystal structure revealed a right‐handed 2₈‐helical conformation with precisely two residues per turn and a helical pitch of 5.8 Å. By 2D ROESY experiments, molecular dynamics simulations, and CD spectroscopy we were able to identify the 2₈‐helix as the predominant conformation in organic solvents. In aqueous solution, the α‐aminoxy peptides exist in the 2₈‐helical conformation at acidic pH, but exhibit remarkable changes in the secondary structure with increasing pH. The most cytotoxic α‐aminoxy peptides have an increased propensity to take up a 2₈‐helical conformation in the presence of a model membrane. This indicates a correlation between the 2₈‐helical conformation and the membranolytic activity observed in mode of action studies, thereby providing novel insights in the folding properties and the biological activity of α‐aminoxy peptides.     

Roseabol A,a New Peptaibol from the Fungus Clonostachys rosea

A new 11 amino acid linear peptide named roseabol A (1) and the known compound 13-oxo-trans-9,10-epoxy-11(E)-octadecenoic acid (2) were isolated from the fungus Clonostachys rosea. Combined NMR and MS analysis revealed that roseabol A (1) contained amino acid residues characteristic of the peptaibol family of peptides such as isovaline, α-aminoisobutyric acid, hydroxyproline, leucinol, and an N-terminal isovaleric acid moiety. The amino acid sequence was established by a combination of NMR studies and tandem MS fragmentation analyses, and the absolute configurations of the constituent amino acids of 1 were determined by the advanced Marfey’s method. Compound 2 showed inhibitory activity against Merkel cell carcinoma, a rare and difficult-to-treat type of skin cancer, with an IC₅₀ value of 16.5 μM.     

Proteome Analysis and In Vitro Antiviral,Anticancer and Antioxidant Capacities of the Aqueous Extracts of Lentinula edodes and Pleurotus ostreatus Edible Mushrooms

In this study, we examined aqueous extracts of the edible mushrooms Pleurotus ostreatus (oyster mushroom) and Lentinula edodes (shiitake mushroom). Proteome analysis was conducted using LC-Triple TOF-MS and showed the expression of 753 proteins by Pleurotus ostreatus, and 432 proteins by Lentinula edodes. Bioactive peptides: Rab GDP dissociation inhibitor, superoxide dismutase, thioredoxin reductase, serine proteinase and lectin, were identified in both mushrooms. The extracts also included promising bioactive compounds including phenolics, flavonoids, vitamins and amino acids. The extracts showed promising antiviral activities, with a selectivity index (SI) of 4.5 for Pleurotus ostreatus against adenovirus (Ad7), and a slight activity for Lentinula edodes against herpes simplex-II (HSV-2). The extracts were not cytotoxic to normal human peripheral blood mononuclear cells (PBMCs). On the contrary, they showed moderate cytotoxicity against various cancer cell lines. Additionally, antioxidant activity was assessed using DPPH radical scavenging, ABTS radical cation scavenging and ORAC assays. The two extracts showed potential antioxidant activities, with the maximum activity seen for Pleurotus ostreatus (IC50 µg/mL) = 39.46 ± 1.27 for DPPH; 11.22 ± 1.81 for ABTS; and 21.40 ± 2.20 for ORAC assays. This study encourages the use of these mushrooms in medicine in the light of their low cytotoxicity on normal PBMCs vis à vis their antiviral, antitumor and antioxidant capabilities.     

Determination of Cytotoxic Activity of Sanguinaria canadensis Extracts against Human Melanoma Cells and Comparison of Their Cytotoxicity with Cytotoxicity of Some Anticancer Drugs

Melanoma is an enormous global health burden, and should be effectively addressed with better therapeutic strategies. Therefore, new therapeutic agents are needed for the management of this disease. The aim of this study was the investigation of cytotoxic activity of some isoquinoline alkaloid standards and extracts obtained from Sanguinaria canadensis—collected before, during, and after flowering—against three different human melanoma cells (A375, G361, SK-MEL-3). The cytotoxicity of these extracts was not previously tested on these melanoma cell lines. Determination of alkaloid contents was performed by HPLC-DAD using Polar RP column and mobile phase containing acetonitrile, water, and 1-butyl-3-methylimidazolium tetrafluoroborate. The cytotoxicity of alkaloid standards was investigated by determination of cell viability and calculation of IC₅₀ values. Significant differences were observed in the alkaloids content and cytotoxic activity of the extracts, depending on the season of collection of the plant material. In the Sanguinaria canadensis extracts high contents of sanguinarine (from 4.8543 to 9.5899 mg/g of dry plant material) and chelerythrine (from 42.7224 to 6.8722 mg/g of dry plant material) were found. For both of these alkaloids, very high cytotoxic activity against the tested cell lines were observed. The IC₅₀ values were in the range of 0.11–0.54 µg/mL for sanguinarine and 0.14 to 0.46 µg/mL for chelerythrine. IC₅₀ values obtained for Sanguinaria canadensis extracts against all tested cell lines were also very low (from 0.88 to 10.96 µg/mL). Cytotoxic activity of alkaloid standards and Sanguinaria canadensis extracts were compared with the cytotoxicity of anticancer drugs—etoposide, cisplatin, and hydroxyurea. In all cases except the one obtained for cisplatin against A375, which was similar to that obtained for Sanguinaria canadensis after flowering against the same cell line, IC₅₀ values obtained for anticancer drugs were higher than the IC₅₀ values obtained for sanguinarine, chelerythrine, and Sanguinaria canadensis extracts. Our results showed that Sanguinaria canadensis extracts and isoquinoline alkaloids, especially sanguinarine and chelerythrine, could be recommended for further in vivo experiments in order to confirm the possibility of their application in the treatment of human melanomas.     

Novel 5H-[1,2,4]oxadiazolo[4,5-a]pyrimidin-5-one derivatives as antibacterial and anticancer agents: Synthesis and biological evaluation

A novel class of 5H-[1,2,4]oxadiazolo[4,5-a]pyrimidine derivatives was prepared, characterized, and tested for its antibacterial and anticancer potential against thirteen strains and five human cancer cell lines. The synthetic method was optimized, and a proposed reaction mechanism was also presented. The compounds containing the 5-bromo-pyrimidine moiety exhibited moderate antibacterial potencies against Gram-positive strains. Furthermore, the newly prepared compounds displayed selectively antiproliferative activity against human cancer cell lines. These current results will help us to further optimize and develop new drug candidates for clinical studies as novel antibacterial or anticancer agents.     

Cannabis-Derived Compounds Cannabichromene and Δ9-Tetrahydrocannabinol Interact and Exhibit Cytotoxic Activity against Urothelial Cell Carcinoma Correlated with Inhibition of Cell Migration and Cytoskeleton Organization

Cannabis sativa contains more than 500 constituents, yet the anticancer properties of the vast majority of cannabis compounds remains unknown. We aimed to identify cannabis compounds and their combinations presenting cytotoxicity against bladder urothelial carcinoma (UC), the most common urinary system cancer. An XTT assay was used to determine cytotoxic activity of C. sativa extracts on T24 and HBT-9 cell lines. Extract chemical content was identified by high-performance liquid chromatography (HPLC). Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and cell cycle, using stained F-actin and nuclei. Scratch and transwell assays were used to determine cell migration and invasion, respectively. Gene expression was determined by quantitative Polymerase chain reaction (PCR). The most active decarboxylated extract fraction (F7) of high-cannabidiol (CBD) C. sativa was found to contain cannabichromene (CBC) and Δ9-tetrahydrocannabinol (THC). Synergistic interaction was demonstrated between CBC + THC whereas cannabinoid receptor (CB) type 1 and type 2 inverse agonists reduced cytotoxic activity. Treatments with CBC + THC or CBD led to cell cycle arrest and cell apoptosis. CBC + THC or CBD treatments inhibited cell migration and affected F-actin integrity. Identification of active plant ingredients (API) from cannabis that induce apoptosis and affect cell migration in UC cell lines forms a basis for pre-clinical trials for UC treatment.     

Synthesis,XRD, spectral,structural, quantum mechanical and anticancer studies of di(p-chlorobenzyl) (dibromo) (1, 10-phenanthroline) tin (IV) complex

The tin complex di (p-chlorobenzyl) (dibromo) (1, 10-phenanthroline) tin (IV) (4CLBR) was synthesised and subjected to characterization using spectroscopic techniques like FT-IR, Raman, ¹HNMR, ¹³CNMR, ¹¹⁹SnNMR, and crystallography. DFT method was used to compare theoretical and experimental results, and the theoretical method was done by the B3LYP/LanL2DZ. The VEDA programme package was used to design the entire vibrational spectral investigation. The Multiwfn software package was used to calculate the quantum chemical equations. A 2D network (C–H–Cl (C–Cl–H-benzyl, interactions forming a 2D network) and hydrogen bonding formed by bromine atoms such as C–H–Br (Sn–Br–H-Phen) were confirmed by X-rays as the complex and crystallisation. The crystal structure of the complex 4CLBR reveals that the tin atom is in a regular octahedral configuration. At the end of the day, anticancer activity has been investigated in this complex using a variety of cell lines, including PC3 (human prostate cancer cell), MCF7 (breast cancer cell), U937 (blood cancer cell), and U87 (brain cancer cell). The anticancer activity results clearly show that the complex 4CLBR and cisplatin have the same anticancer activity at concentrations of 15.6 g/ml against the U87 cell line.     

Design and synthesis of novel 7-[(N-substituted-thioureidopiperazinyl)-methyl]-camptothecin derivatives as potential cytotoxic agents

Abstract

As part of continuing our research on diverse C-7 derivatives of camptothecin (CPT), 16 CPT derivatives bearing piperazinyl-thiourea chemical scaffold and different substituent groups have been designed, synthesized and evaluated in vitro for cytotoxicity against five tumor cell lines (A-549, MDA-MB-231, MCF-7, KB and KBvin). As a result, all the synthesized compounds showed promising in vitro cytotoxic activity against the five tumor cell lines tested, and were more potent than irinotecan. Importantly, compounds 13?g (IC₅₀ = 0.514?μM) and 13o (IC₅₀ = 0.275?μM) possessed similar or better antiproliferative activity against the multidrug-resistant (MDR) KBvin subline than that of topotecan (IC₅₀ = 0.511?μM) and merit further development as anticancer candidates for clinical trail. With these results in hand, we have a reason to conclude that incorporating piperazinyl-thiourea motifs into position-7 of camptothecin confers well cytotoxic activity against cancer cell lines, probably resulting in new anticancer drugs.     

Phytochemical Analysis,Antioxidant and Anticancer Potential of Sideritis niveotomentosa: Endemic Wild Species of Turkey

Sideritis niveotomentosa Hub. -Mor. is a local endemic species belonging to the Lamiaceae family. In this study, GC/MS analysis, total antioxidant capacity and anticancer effects of different extracts obtained from S. niveotomentosa were investigated comparatively. Total phenolic contents of extracts were determined by the Folin–Ciocalteu method, total flavonoid contents by aluminum chloride method, and also the free radical scavenging activities of the extracts by DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay. The cytotoxic effect of the extracts was studied via MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay on DLD1, HL60 and ARH77 cell lines. Pro-apoptotic gene expression levels were also tested in the most sensitive cell line ARH77 by Real-Time PCR. The expression levels of 4 pro-apoptotic genes, APAF, BAX, CASP3, and HRK were found to be upregulated in ARH77 cells that were treated extracts. Results showed that methanolic extracts contain more phenolic content than acetone extracts, consistent with DPPH results. As a result, Sideritis niveotomentosa extracts, especially methanolic extracts, are rich in phenolic content and have a strong radical scavenging effect. In addition, the extracts showed selective effects on cell lines. This study is pioneering in terms of future studies, and the findings provide hope for future experimentation.     

Chemical Composition,Antioxidant and Anticancer Activities of Leptocarpha rivularis DC Flower Extracts

An evaluation of antioxidant and anticancer activity was screened in Leptocarpha rivularis DC flower extracts using four solvents (n-hexane (Hex), dichloromethane (DCM), ethyl acetate (AcOEt), and ethanol (EtOH)). Extracts were compared for total extract flavonoids and phenol contents, antioxidant activity (2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), ferric reducing antioxidant potential (FRAP), total reactive antioxidant properties (TRAP) and oxygen radical absorbance capacity (ORAC)) across a determined value of reduced/oxidized glutathione (GSH/GSSG), and cell viability (the sulforhodamine B (SRB) assay). The most active extracts were analyzed by chromatographic analysis (GC/MS) and tested for apoptotic pathways. Extracts from Hex, DCM and AcOEt reduced cell viability, caused changes in cell morphology, affected mitochondrial membrane permeability, and induced caspase activation in tumor cell lines HT-29, PC-3, and MCF-7. These effects were generally less pronounced in the HEK-293 cell line (nontumor cells), indicating clear selectivity towards tumor cell lines. We attribute likely extract activity to the presence of sesquiterpene lactones, in combination with other components like steroids and flavonoids.     

A new bioactive prenylated dihydroflavanoid from Dolichos tenuicaulis （Baker） Craib

A new prenylated dihydroflavonoid was obtained from the root of Dolichos tenuicaulis （Baker） Craib. The structure was elucidated as （2S）-5,2＇,6＇-trihydroxy-3＇″, 8-di （γ,γ-dimethyl-allyl）-2＇″, 2＇″-dimethylpyrano-[5＇″,6＇″： 6,7]-2＇″″,4＇″″-cyclohexadiene-1 ＇″″-one-[2＇″″,3＇″″： 3＇,4＇]-flavanone, named dolichnin A, by spectroscopic methods including UV, IR, HR-EI-MS, 1D NMR and 2D NMR techniques, and subsequently, the anticancer activity of this compound to inhibit human cancer cells＇ growth including A549, BEL-7402, Hep-3B, SMMC7721, HT-29, MCF-7, SGC-7902, K562, A498 and PC3 cell lines by MTT method was evaluated in vitro.     

Concurrent Reactive Oxygen Species Generation and Aneuploidy Induction Contribute to Thymoquinone Anticancer Activity

Thymoquinone (TQ) is the main biologically active constituent of Nigella sativa. Many studies have confirmed its anticancer actions. Herein, we investigated the different anticancer activities of, and considered resistance mechanisms to, TQ. MTT and clonogenic data showed TQ’s ability to suppress breast MDA-MB-468 and T-47D proliferation at lower concentrations compared to other cancer and non-transformed cell lines tested (GI₅₀ values ≤ 1.5 µM). Flow-cytometric analyses revealed that TQ consistently induced MDA-MB-468 and T-47D cell-cycle perturbation, specifically inducing pre-G1 populations. In comparison, less sensitive breast MCF-7 and colon HCT-116 cells exhibited only transient increases in pre-G1 events. Annexin V/PI staining confirmed apoptosis induction in MDA-MB-468 and HCT-116 cells, which was continuous in the former and transient in the latter. Experiments revealed the role of reactive oxygen species (ROS) generation and aneuploidy induction in MDA-MB-468 cells within the first 24 h of treatment. The ROS-scavenger NAD(P)H dehydrogenase (quinone 1) (NQO1; DT-diaphorase) and glutathione (GSH) were implicated in resistance to TQ. Indeed, western blot analyses showed that NQO1 is expressed in all cell lines in this study, except those most sensitive to TQ-MDA-MB-468 and T-47D. Moreover, TQ treatment increased NQO1 expression in HCT-116 in a concentration-dependent fashion. Measurement of GSH activity in MDA-MB-468 and HCT-116 cells found that GSH is similarly active in both cell lines. Furthermore, GSH depletion rendered these cells more sensitive to TQ’s antiproliferative actions. Therefore, to bypass putative inactivation of the TQ semiquinone metabolite, the benzylamine analogue was designed and synthesised following modification of TQ’s carbon-3 atom. However, the structural modification negatively impacted potency against MDA-MB-468 cells. In conclusion, we disclose the following: (i) The anticancer activity of TQ may be a consequence of ROS generation and aneuploidy; (ii) Early GSH depletion could substantially enhance TQ’s anticancer activity; (iii) Benzylamine substitution at TQ’s carbon-3 failed to enhance anticancer activity.     

Oak gum mediated green synthesis of silver nanoparticles under ultrasonic conditions: Characterization and evaluation of its antioxidant and anti-lung cancer effects

Herein, we represent the bio-synthesis of silver nanoparticles (Ag NPs) employing Oak gum as the green template, an efficient natural and non-toxic reductant and stabilizer based on its phytochemicals by using ultrasonic irradiation. The characterization of as-synthesized Ag NPs was performed through Fourier transformed infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), elemental mapping, UV–Vis and X-ray diffraction (XRD). After the characterization, the synthesized Ag NPs/O. Gum was engaged in biological assays like study of anti-oxidant properties by DPPH mediated free radical scavenging test using MeOH and BHT as reference molecules. Thereafter, on having a significant IC₅₀ value in radical scavenging assay, we extended the bio-application of the desired nanocomposite in anticancer study of A549, Calu6 and H358 human lung cell lines in-vitro through MTT assay. They had very low cell viability and high anti-human lung cancer activities dose-dependently against the cell lines without any cytotoxicity on the normal cell line (MRC-5). The IC₅₀ of Ag NPs/O. Gum was found 161.25, 289.26 and 235.29 µg/mL against A549, Calu6 and H358 cell lines, respectively. Maybe significant anti-human lung cancer potentials of Ag NPs/O. Gum against common lung cancer cell lines are related to their antioxidant activities. So, these results suggest that synthesized Ag NPs/O. Gum as a chemotherapeutic nanomaterial have a suitable anticancer activity against lung cell lines.     

Design,synthesis and molecular modeling studies of few chalcone analogues of benzimidazole for epidermal growth factor receptor inhibitor in search of useful anticancer agent

In the present investigation, few 3-(substitutedphenyl)-1-[2-(1-hydroxy-ethyl)]-1H-benzimidazol-1-yl)prop-2-en-1-ones are EGFR antagonist are designed, by molecular docking analysis. The synthesized compounds were tested for their in vitro anticancer activity by propidium iodide fluorescent assay and Trypan blue viability assay against colorectal cancer cell lines (HCT116) and non-small cell lung cancer cell lines (H460). Human Epithelial Kidney cell lines (HEK) are used as normal cell lines for studying effect of drug on non-cancerous cells within human body. Evaluation of cytotoxic studies of synthesized compounds CHL(1–8) reveal that compound CHL1 [IC₅₀ = 7.31 and 10.16 μM against HCT116 and H460 cell lines respectively, by PI assay] and CHL8 [IC₅₀ = 12.52 and 6.83 against HCT116 and H460 μM cell lines respectively] possess promising cytotoxic activity.     

Synthesis of Bis‐acridine Derivatives Exhibiting Anticancer and Anti‐inflammatory Activity

A series of bis‐acridine derivatives 3a – j and 5a – j have been synthesized by condensation of 9‐chloro‐2,4‐(un)substituted acridines (1a – e) and 9‐isothiocyanato‐2,4‐(un)substituted acridines (4a – e) with diamine 2a and 2b , respectively. These bis‐acridines were evaluated in vitro for activity against a panel of human cancer cell lines of lung (NCI H‐522), ovary (PA1), breast (T47D), colon (HCT‐15), and liver (HepG2). Several bis‐acridines were found to possess good anticancer activity against various cancer cell lines. Of these, compound 3h exhibited good anticancer activity against all cancer cell lines tested except liver (HepG2) cell line. In addition to this, these compounds were screened for anti‐inflammatory activity at a dose of 50 mg/kg p.o. Compound 3g exhibited 41% anti‐inflammatory activity, which is better than most commonly used standard drug ibuprofen, which showed 39% anti‐inflammatory (at 50 mg/kg p. o.) activity.     

Synthesis of 2-(2,3,4-trimethoxyphenyl)-1-(substituted-phenyl)acrylonitriles: in vitro anticancer activity against MCF-7, PC-3 and A2780 cancer cell lines

A series of 2-(2,3,4-trimethoxyphenyl)-1-(substituted-phenyl)acrylonitrile (2–9) were designed and synthesized to develop new cancer drugs. The structures of synthesized compounds 2–9 were described by using melting point, mass (MALDI-TOF-MS), FT-IR, elemental analysis, ¹H, ¹³C, ¹³C-APT and 2D NMR spectroscopy. The in vitro anticancer activities of 2–9 against human breast cancer (MCF-7), human prostate cancer (PC-3) and human ovarian cancer cells (A2780) were investigated by [3-(4,5-dimethylthiazol)-2-yl]-2,5-diphenyl-2H-tetrazolium bromide] (MTT) assay method. Additionally, the LogIC₅₀ values of these compounds on A2780, MCF-7 and PC-3 cell lines were calculated by using inhibition % values by the GraphPad Prism 6 program on a computer. The results indicated that these compounds have high anticancer activity against MCF-7, PC-3 and A2780 cell lines (especially A2780 cell lines, p < 0.05).