Leuprorelin® (LEP) is an FDA drug for breast cancer and prostate cancer treatment. There are several reported adverse effects such as transient hyper- tension, excessive salivation, and increased dysuria during treatment with LEP. In this study, the efficacy and toxicity of LEP were modified by using a drug delivery system to adjust the physicochemical properties. In this regard, Leuprorelin® conjugates of triphenylmethanol derivatives (TPMs) were syn- thesized as prodrugs. Comparative antiproliferative assays showed that LEP-TPMs conjugates had significantly higher antiproliferativeactivities than the corresponding non-covalent physical mixtures of the TPMs and LEP against human invasive ductal carcinoma (BT549), human prostate carci- noma (PC3), human lung cancer (A549) and mouse pre-adipocytes (3T3-L1) cells.
The present study indicates that white sesame seeds, with high total contents of phenolics and avonoids, have signicant antioxidant and antiproliferativeactivities. Interestingly, signicant correlations between ORAC values and total pheno- lics were observed in the current study. A signicant portion of phenolic compounds, antioxidant and antiproliferative activi- ties of sesame seed extracts were found in the free fractions. In general, white sesame seeds have promising potential in the development of natural antioxidants and functional foods. Therefore, further studies on the mechanisms of action of antioxidant and antiproliferativeactivities of white sesame seed extracts are needed in the future.
The human body possesses numerous antioxidant de- fences and repair mechanisms against oxidative stress. However, these mechanisms are insufficient to prevent the damage entirely as production of reactive oxygen species (ROS) is certain to play multiple important roles in tissue damage and loss of function in a number of tis- sues and organs . Free radicals and ROS have been implicated as endogenous initiators in the etiology of cancer and several other degenerative or pathologic pro- cesses of various serious diseases, as well as in aging processes . Oxidative damage to DNA is considered a critical step in cancer development . Over the past decade or so, numerous experimental and epidemio- logical studies have shown that a wide variety of phyto- chemicals such as phenolics, flavonoids, isoflavone, flavones, anthocyanins, catechin, isocatechin and carot- enoids are able to prevent or slow down oxidative stress- induced damage leading to carcinogenesis by upsetting the molecular events in the initiation, promotion or pro- gression conditions. Recent studies demonstrated that the high dietary intake of fruits and vegetables could be associated with lower cancer prevalence in humans [4-7]. Natural products mainly from plant kingdom offer a wide range of biologically active compounds that act as natural antioxidants with recognized potential in drug discovery and development . Great interest is cur- rently being paid to natural products for their interesting anticancer activities. High percentages (~ 60%) of all the drugs applied in the treatment and/or prevention of can- cer are from natural products and their derivatives, of which higher plants contribute around 25%. Approxi- mately 60% of drugs approved for cancer treatment are of natural origin [9,10]. This has elicited the pursuit of effective antioxidant and anticancer agents from various sources particularly medicinal and edible plants . Investigations on natural products have regained prom- inence in the recent past with increasing understanding of their biological significance such as antioxidant, rad- ical scavenging, antiproliferativeactivities and increasing recognition of the origin and function of their structural diversity [12-15].
of the bacterial membrane and the death of microorganisms. Furthermore, just like traditional photosensitizers, which have been widely applied in photodynamic therapy, titanate contain- ing silver can also release highly reactive ROS to incapacitate the bacteria as well. For titanate nanofibers containing silver, the prolonged time of UV light irradiation may cause the formation of more silver nanoparticles on the surface of titanate nanofi- bers. However, this effect has been shown to be insignificant due to the relatively slow reduction process induced by UV light, which usually takes more than 10 hours. More interestingly, the as-prepared titanate nanocomposites containing silver also demonstrated good antiproliferativeactivities when tested in the human liver cancer cell line Hep G2 as a model target. As indi- cated in Figure 6B, both Ag 2 Ti 5 O 11 ⋅ xH 2 O and Ag/titanate (UV light irradiation) have better antiproliferative effects than those observed with Ag/titanate (NaBH 4 reduction) and plain titanate nanofibers, with the IC 50 values being 32.28 and 37.51 µ g/mL, respectively, without UV light irradiation. Moreover, the IC 50 values can be further lowered to 4.79 and 2.53 µ g/mL due to ROS-mediated cell damage; this is consistent with the antifun- gal activities discussed above. These promising antiproliferativeactivities of the inorganic titanates containing silver are also comparable to those found with purely organic drugs such as mitomycin C (MMC, C 15 H 18 N 4 O 5 ); the IC 50 values were 10.16 µ g/mL (with UV light irradiation) and 12.21 µ g/mL (without UV light irradiation), respectively.
E Drechslera spp. Fusarium spp. and Colletotrichum spp. , one from the Stem i.e Helminthosporium spp. and three from the roots included -Bispora spp. Alternaria spp. Dematious hyphomycetes spp. All these were isolates were studied for their antiproliferativeactivities. The cytotoxicity of all isolates was tested on HeLa and MCF7 cell lines. Endophytic fungal extracts showed the cytotoxicity which varied from 10% to 80%. The isolates from leaf-2 and root –2, shown the highest activity against HeLa cell line. The cytotoxicity of endophytes varied from
Medicinal plants serve as unlimited source for phytoconstituents that possess potent antioxidant and antiproliferative properties. Artemisia nilagirica L. is a potent medicinal plant widely found in India and has been used to treat human diseases for centuries. The present investigation was conducted to investigate the antioxidant and antiproliferative abilities of different crude extracts of A. nilagirica. A detailed study was performed on the antioxidant activity and antiproliferative activity of the methanol extract of A. nilagirica by in vitro chemical analysis. The chemical composition of extracts, studied in terms of phenolics, total ﬂavonoids, triterpenoids, tannins and alkaloids were also determined. Results suggested that the amounts of different phytoconstituents in extracts vary based on polarity of solvents. The extracts possessed different antioxidant and radical-scavenging activities in different assays. Among the extracts, ethyl acetate and alcohol extracts showed the most potent radical-scavenging activities. Ethyl acetate and alcohol extracts showed cytotoxicity towards eight different human cancer cell lines in vitro with IC 50 values ranging between 30.43±0.86 and 982.46±14.40 μg/ml and they were less toxic to normal cell lines. The findings of this study provide evidence that A. nilagirica extracts can be used potentially as ready accessible and valuable bioactive source for isolation of antioxidant and anticancer agents.
Background: Free radical-induced oxidative stress is the root cause for many human diseases. Naturally occurring antioxidant supplements from plants are vital to counter the oxidative damage in cells. The main objective of the present study was to characterize the antioxidant and antiproliferative potential of rice bran extracted from an important Indian rice variety, Njavara and to compare the same with two commercially available basmati rice varieties: Vasumathi, Yamini and a non medicinal variety, Jyothi.
Methods: The air-dried flowers of Anthemis palestina were subjected to hydrodistillation to yield the oil. The antioxidant activity of the hydrodistilled oil was characterized using various in vitro model systems such as DPPH, ferric-reducing antioxidant power and hydroxyl radical scavenging activity. Antibacterial activity was tested against six bacterial species, representing both Gram positive and Gram negative bacteria. Antifungal activity was evaluated using three Candida species. The minimum inhibitory concentration (MIC) for each examined microorganism was determined using the microdilution method. The oil ’ s antiproliferative effects against eight human cancer cell lines were also studied and the lethal doses that resulted in 50% reduction of cell viability (LD 50 ) were determined.
The in vitro antiproliferative assay was performed according to Monks et al. . Also, The human kera- tinocyte cell line HaCaT, kindly donated by Dr. Ricardo Della Coletta (FOP, UNICAMP, Piracicaba, SP, Brazil), murine normal fibroblast (3T3) and eight human tumor cell lines [glioma (U251), melanoma (UACC-62), breast (MCF-7), multidrug resistant ovarian (NCI-ADR/RES), kidney (786–0), lung, non-small cells (NCI-H460), pros- tate (PC-3), and ovarian (OVCAR-03)], kindly provided by the National Cancer Institute (Frederick, MD, USA), were used in this study. Stock and experimental cultures were grown in medium containing 5 mL RPMI 1640 (Gibco BRL, Gaithersburg, MD, USA) supplemented with 5% fetal bovine serum (Gibco BRL). Peniciline: streptomicine mixture (1000 U/mL:1000 μg/mL, 1 mL/L RPMI) was added to the experimental cultures. In 96-well plates, 100 μL cells/well of each cell line aforementioned were exposed to EEGP and HF at the concentrations of 0.25, 2.5, 25, and 250 μg/mL in dimethyl sulfoxide (DMSO)/RPMI, vehicle control, or doxorubicin (Dox) used as positive control (0.25, 2.5, 25, and 250 μg/mL), at 37°C, 5% CO 2 aerobically for 48 h. Final DMSO concen-
bated with 50 μL of medium containing various concentra- tions of either crude extract or fraction, and the cell cultures were incubated for 48 h. The crude extract or frac- tion was first pre-suspended in DMSO and then diluted in DMEM media. Control cell cultures were incubated with DMSO (final concentrations of DMSO 0.06%-0.5%). Con- trol cell cultures did not show any evidence of cell damage. In the last 4 h of the cell culture, 10 μL of MTT stock solu- tion (5 mg/mL) were added to each well. Formazan crystals were dissolved with acidic isopropanol, and the plates were read in an ELISA plate reader, using a test wavelength of 570 nm and a reference wavelength of 630 nm. Plates were normally read within 15 min of adding isopropanol. The antiproliferative activity of extracts was reported as IC 50
In order to determine the chemical composition of the hydroalcoholic extract obtained from the stems of the Lebanese plant Ephedra campylopoda, a phytochemical screening was carried out. The latter aids in identifying the content of this extract in primary and secondary metabolites in order to study and for the first time, some of the biological activities (as the antioxidant, antiproliferative and antibacterial) of this plant. The obtained results showed that the stems of Ephedra campylopoda are rich in several bioactive molecules such as polyphenols, flavonoids, tannins, etc. This wealth presented a remarkable antioxidant activity at a concentration of 0.5 mg/mL. It also presented an antiproliferative effect on two types of cancer cells: epithelial HT-29 and human colon HCT-116. Finally, its antibacterial effect was noticed against five bacterial strains. The obtained results encourage further research to be conducted in order to confirm the antibacterial, antioxidant and antiproliferative effects of this Lebanese plant.
Abstract: This research work deals with the design and synthesis of a series of substituted phenylfuranylnicotinamidines 4a–i. Facile preparation of the target compounds was achieved by Suzuki coupling-based synthesis of the nitrile precursors 3a–i, followed by their conversion to the corresponding nicotinamidines 4a–i utilizing LiN(TMS) 2 . The antimicrobial activities of the newly synthesized nicotinamidine derivatives were evaluated against the Gram-negative bacterial strains Escherichia coli and Pseudomonas aeruginosa as well as the Gram-positive bacterial strains Staphylococcus aureus and Bacillus megaterium. The minimum inhibitory concentration values of nicotinamidines against all tested microorganisms were in the range of 10–20 µM. In specific, compounds 4a and 4b showed excellent minimum inhibitory concentration values of 10 µM against Staphylococcus aureus bacterial strain and were similar to ampicillin as an antibacterial reference. On the other hand, selected nicotinamidine derivatives were biologically screened for their cytotoxic activities against a panel of 60 cell lines representing nine types of human cancer at a single high dose at National Cancer Institute, Bethesda, MD, USA. Nicotinamidines showing promising activities were further assessed in a five-dose screening assay to determine their com- pound concentration causing 50% growth inhibition of tested cell (GI 50 ), compound concentration causing 100% growth inhibition of tested cell (TGI), and compound concentration causing 50% lethality of tested cell (LC 50 ) values. Structure-activity relationship studies demonstrated that the activity of members of this series can be modulated from cytostatic to cytotoxic based on the substitution pattern/nature on the terminal phenyl ring. The most active compound was found to be 4e displaying a submicromolar GI 50 value of 0.83 µM, with TGI and LC 50 values of 2.51
ABSTRACT: Objective: To evaluate the chemical composition, antioxidant and antiproliferativeactivities of Hyptis pectinata aerial part aqueous extract (HYP). Method: Chemical profiling using high-performance liquid chromatography with UV diode array detector (HPLC-UV-DAD), in-vitro antioxidant and anti-proliferative studies were done. Antioxidant and antiradical activities of HYP was investigated using 3-(4,5- dimethylimidazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and DPPH radical scavenging assay. Result: The present study revealed several metabolites. HPLC analysis gave caffeic acid (13.92%), rutin (7.89%) and ferulic acid (5.44%) as some of the bioactive constituents. HYP showed antioxidant activity in both the DPPH and MTT assay. HYP exhibited antioxidant activity against DPPH and MTT from the first dilution at 10 mg/ml up to the ninth dilution at 0.08 mg/ml in a 2-fold dilution signifying the presence of antioxidant compounds at those concentrations. At 1 mg/ml to 32 mg/ml, HYP dose-dependently and significantly (P < 0.001) inhibited Sorghum bicolor seed radicle growth throughout 24-72 h compared to the negative control. Conclusion: Hyptis pectinata aerial part aqueous extract (HYP) possessed antioxidant and antiproliferativeactivities, hence providing preliminary evidence for its use to treat cancer.
In summary, we have synthesized a series of TQ analogues and evaluated their antiproliferativeactivities against ovarian cancer cell lines and human malaria parasite. The TQ analogues 6 and 14 had significant inhibitory activities that doubled that of TQ. Compound 6 and 2,5-di-tert-butyl-1,4-benzoquinone (13) show the most potent antiplasmodial activity. Furthermore, the improved solubility of compound 6 together with its synthetic tractability warrants additional SAR studies of other analogues (e.g. monoalkylamino, dialkylamino, and cyclicamino groups) in order to find lead compounds with significantly improved antiproliferativeactivities against ovarian cancer cell lines.
Broch et al, designed and synthesized Dimeric and trimeric analogues of 2,3 substituted quinoline derivatives and evaluated them for their in vitro antiproliferativeactivities toward a human fibroblast primary culture and two human solid cancer cell lines (MCF-7 breast and PA 1, ovarian carcinoma). Results showed that the dimeric analogous (2,2′ Dimethoxy-3,7′-biquinoline (XVIII) and 2,2′-Diethoxy- 3,7′-biquinoline ( XIX) are slightly active toward PA1 and MCF-7 cell lines with IC 50 values in the range of 36–54 μM,
The compound, ESAr induces antiangiogenic, antiproliferativeactivities and apoptosis in murine melanoma cells B16F10 and human melanoma cells A375 but has shown no toxicity or inhibition of proliferation against normal cell like mouse skin fibroblast. Dual staining of annexin V/propidium iodide (PI) showed that ESAr treatment significantly increased apoptotic cells in both melanoma cell lines but had no effect on non cancerous fibroblast cells. FACS analysis data with wild type p53 revealed that in presence of ESAr (50M) the p53 expression level increased with time of ESAr-exposure. p53 is a tumor suppressor protein which induces apoptosis, cell cycle arrest, and angiogenesis in response to genotoxic and other stresses. Net (Elk3 /ERP/Sap-2) can act both as an activator and a repressor of transcription and has been shown to regulate the angiogenic switch, by regulating VEGF expression. Down-regulation of Net and VEGF mRNA expressions were shown to inhibit angiogenesis here. In other case Cyclin D (member of the cyclin family of cell cycle regulators) modulates the activity of Cyclin dependent kinases which are considered a potential target for anti-cancer medication, was inhibited at mRNA level. ESAr induces inhibition of invasion in B16F10 and slower migration in A375 cell lines.
Combretastatin A‑4 is a highly potent natural stilbene that can inhibit cancer cell proliferation. Numerous analogues of combretastatin A‑4 have been proposed for clinical applications. However, structural studies of combretastatin A‑2, a methylenedioxy derivative of combretastain A‑4, are not available. In this study, various analogues of combretastatin A‑2 with polymethylenedioxy spacer were prepared and their antiproliferativeactivities to four human cancer cell lines (HeLa, SK‑OV‑3, A549, and HT‑29) and two normal cells (HaCaT and MDCK) were evaluated. Binding characteris‑ tics were evaluated based on computational docking and previously reported experimental data. Results suggest that their binding conformations are highly dependent on steric volume and electrostatic properties of substituents. Keywords: Polymethylenedioxy, Combretastatin, Computational docking, Antiproliferative activity, Stilbene
Background: Studies have shown that the barks and roots of some Apocynaceae species have anticancer and antimalarial properties. In this study, leaf extracts of five selected species of Apocynaceae used in traditional medicine (Alstonia angustiloba, Calotropis gigantea, Dyera costulata, Kopsia fruticosa and Vallaris glabra) were assessed for antiproliferative (APF) and antiplasmodial (APM) activities, and analysed for total alkaloid content (TAC), total phenolic content (TPC) and radical-scavenging activity (RSA). As V. glabra leaf extracts showed wide spectrum APF and APM activities, they were further screened for saponins, tannins, cardenolides and terpenoids.
To our knowledge, this is the first study to use such a large collection of clinical drugs to test antiproliferative effect in ACC cells. These findings support the utility of qHTS of clinical drug library as a feasible approach for screening drug activity in other cancer cell lines from various other solid and hematologic malignancies. Be- cause the costs and resources required for developing a new drug for rare cancers, such as ACC, are often pro- hibitive, the qHTS is an excellent, relatively inexpensive approach to identify effective agents in a short period of time. The discovery of new anticancer drugs using well- known compounds has several important implications. Patients with locally advanced and/or metastatic ACC could benefit from the identification of clinically approved agents that show anticancer effect specific to ACC cells and the prompt development of clinical trials to test the efficacy of these compounds can be initiated in relatively shorter time compared to the time required to bring unapproved compounds to clinical trials. An in vivo testing may still be necessary to identify the most effective drugs and or combination and to assess the dif- ferent toxicity profile generated by drug combination treatment. Because drug toxicity is a common reason for discontinuation of therapy and poor compliance to the treatment, screening of existing drugs for new activity may be helpful because the toxicity of these drugs is well characterized and the most effective agents with the low- est toxicity profile can be selected. The toxicity may also be predicted and mitigated by using various countermea- sures known for specific drugs. Furthermore, agents with clinical achievable concentrations can be determined after qHTS and the selection of those agents with potent activity well below the clinical sustained and peak con- centrations of a drug is also a very attractive approach to use for cancer therapeutics. Even drugs that have IC 50
Hydrazones act as very important intermediates in the synthesis of various heterocyclic compounds but in addition to this property they are also very effective organic compounds with important biological activities. When hydrazones are used as intermediates various coupling products can be synthesized by using the active hydrogen component of azomethine group (– CONHN=CH). Large number of biologically active compounds can be synthesized by researchers, for example: iproniazide and isocarboxazide are synthesized by hydrazones reduction. Iproniazide have structure similar to isoniazid that’s why used in the treatment of tuberculosis. In some patients it also shows an antidepressant and mood changing effect. Another example of clinically effective hydrazones is nifuroxazide used as an intestinal antiseptic 4 .