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Orthosiphon stamineus (O.S) is widely consumed for its medidcinal value including anti-inflammatory, anti-infective, and diuretic properties. The present study evaluates the cytoprotective, anti-mutagenic, and anticlastogenic efficacies of standardized extract of Orthosiphon stamineus. Normal liver cell line (WRL68) exposed to hydrogen peroxide and serum-deprived media as insults to evaluate cytoprotective and glutathione activation activities of (Et. O. s). Salmonella typhimurium TA98 and TA100 exposed to different concentrations of (Et. O. s). The influence of Et. O. s on mitotic, replicative indices as well as chromosomal aberration (CA) and sister chromatid exchange (SCE) induced in human peripheral blood lymphocytes by mitomycin C (MMC). The Et. O.s proved to be a potent scavenger for hydrogen peroxide and other free radicals in serum-depraved media, which showed to stimulate glutathione production in liver cells line. Moreover, it did not induce mutations in S. typhimurium subspecies TA98 and TA100. The standardized extract exhibited powerful antimutagenic activities as verified against both 2-nitrofluorene and sodium azide in S. typhimurium TA98 and TA100 cells, respectively. Cytogenetic tests showed high concentrations of Et. O. s to reduce the values of mitotic and replicative indices without any accompanying side effects, such as chromosomal abnormalities or SCE. To ameliorate MMC effects, pretreatment with the extract proofed to be efficient protocol. These data suggests that O. stamineus extract could be useful as cytoprotective, antimutagenic, and anticlastogenic efficacies, which owes to its potent chemoprevention, antioxidant, and glutathione activation properties.

Beta-Caryophyllene (BCP), a naturally occurring sesquiterpene abundantly found in cloves, hops, and cannabis, is the active candidate of a relatively new group of vascular-inhibiting compounds that aim to block existing tumor blood vessels. Previously, we have reported the anti-cancer properties of BCP by utilizing a series of in-vitro anti-tumor-related assays using human colorectal carcinoma cells. The present study aimed to investigate the effects of BCP on in-vitro, ex-vivo, and in-vivo models of anti-angiogenic assays and evaluate its anti-cancer activity in xenograft tumor (both ectopic and orthotopic) mice models of human colorectal cancer. Computational structural analysis and an apoptosis antibody array were also performed to understand the molecular players underlying this effect. BCP exhibited strong anti-angiogenic activity by blocking the migration of endothelial cells, tube-like network formation, suppression of vascular endothelial growth factor (VEGF) secretion from human umbilical vein endothelial cells and sprouting of rat aorta microvessels. BCP has a probable binding at Site#0 on the surface of VEGFR2. Moreover, BCP significantly deformed the vascularization architecture compared to the negative control in a chick embryo chorioallantoic membrane assay. BCP showed a remarkable reduction in tumor size and fluorescence molecular tomography signal intensity in all the mice treated with BCP, in a dose-dependent relationship, in ectopic and orthotopic tumor xenograft models, respectively. The histological analysis of the tumor from BCP-treated mice revealed a clear reduction of the density of vascularization. In addition, BCP induced apoptosis through downregulation of HSP60, HTRA, survivin, and XIAP, along with the upregulation of p21 expressions. These results suggest that BCP acts at multiple stages of angiogenesis and could be used as a promising therapeutic candidate to halt the growth of colorectal tumor cells.

In the present study, two important starting materials and 18 new 1,2,4-triazole compounds with mono ring system have been synthesized and characterized. The mono system showed 16 compounds of a Schiff base moiety attached to the triazole ring which was prepared from the corresponding starting material 5(A–B) or piperidinium salt system 6(A–B). All these compounds were characterized using Fourier Transform Infrared (FT-IR) and Nuclear Magnetic Resonance (NMR) spectroscopy and carbon hydrogen nitrogen (CHN) elemental analysis. The compounds were selected for in vitro anticancer study to test the therapeutic cytotoxic potential against cancer cells. The MTT test was conducted against human breast (MCF-7) and colorectal (HCT-116) cancer cells. Among all the compounds tested, 7A-i demonstrated more pronounced in vitro anticancer effect against MCF-7 and HCT-116 cells with IC50 of 38 and 19.2 μM, respectively, comparable to that of the standard reference drugs, tamoxifen and 5-fluorouracil, respectively. Compound 7A-vi showed a considerable cytotoxic effect with IC50 53 and 41.2 μM against MCF-7 and HCT-116 cells, respectively. Compounds 7A-ii, 7A-iii and 7A-v exhibited moderate cytotoxicity with IC50 68, 91 and 85 μM, respectively against MCF-7 cells and also 59.3, 81.7 and 137.1 μM against HCT-116 cells, respectively. However, all other compounds tested in this study showed poor cytotoxicity against both the cell lines. Cellular morphological analysis revealed that the cytotoxicity induced by the compounds could probably due to autophagy. It can be concluded that 1,2,4-triazole derivatives can be promising therapeutic agents. Further studies will be done to investigate the antitumor efficacy of the 1,2,4-triazole derivatives using suitable preclinical models.

The bidentate N-cyclohexyl-2-(3-hydroxy-4-methoxybenzylidene)hydrazine-1-carbothioamide Schiff base ligand (HL) was coordinated to divalent nickel, palladium and platinum ions to form square planar complexes. The nickel and palladium complexes, [NiL2 ], [PdL2 ] form square planar complexes with 2:1 ligand to metal ratio. The platinum complex, [PtL(dmso)Cl] formed a square planar complex with 1:1 ligand to metal ratio. Platinum undergoes in situ reaction with DMSO before complexing with the ligand in solution. The cytotoxicity of HL, [NiL2 ], [PdL2 ], and [PtL(dmso)Cl] were evaluated against human colon cancer cell line (HCT-116), human cervical cancer (Hela) cell line, melanoma (B16F10) cells, and human normal endothelial cell lines (Eahy926) by MTT assay. The [NiL2 ] complex displayed selective cytotoxic effect against the HCT 116 cancer cell line with IC50 of 7.9 ± 0.2 μM. However, HL, [PdL2 ], and [PtL(dmso)Cl] only exhibited moderate cytotoxic activity with IC50 = 75.9 ± 2.4, 100.0 ± 1.8, and 101.0 ± 3.6 μM, respectively. The potent cytotoxicity of [NiL2 ] was characterized using Hoechst and Rhodamine assays. The nickel complex, [NiL2 ], caused remarkable nuclear condensation and reduction in mitochondrial membrane potential. In addition, molecular docking studies confirms that [NiL2 ] possesses significant binding efficiency with Tyrosine kinase. Altogether, the results revealed that [NiL2 ] exhibits cytotoxicity against the cancer cells via Tyrosine kinase-induced proapoptosis pathway. This study demonstrates that the [NiL2 ] complex could be a promising therapeutic agent against colorectal carcinoma.

Two binuclear selenium adducts (5 and 6) were designed using molecular docking approach while finding their promising interaction to four angiogenic factor-proteins including COX-1 (Cyclooxygenase-1), VEGF-A (vascular endothelial growth factor A), HIF (Hypoxia-inducible factor) and EGF (human epidermal growth factor). They were consequently synthesized using In-situ coordination approach. The green synthetic approach was employed for coordination as it was carried out in water instead of organic solvents. The synthesized adducts as well as their respective bis-benzimidazolium salts (2 and 4) were confirmed by 1H and 13C-NMR along with FT-IR spectroscopy. The both were, then, subjected to In-vitro anticancer activities against breast adenocarcinoma cell line (MCF-7), cervical cancer cell line (Hela), mouse melanoma cell line (B16F10) and retinal ganglion cell line (RGC-5) using MTT assay while comparing their activities with a commercially established standard-drug 5-Fluorouracil. However, the exceptional activities of both adducts and bis-benzimidazolium salts were explored.

NuvastaticTM is a polymolecular botanical drug formulation containing a proprietary extract of a selected cultivar of Orthosiphon stamineus (OS) code name, C5OSEW5050ESA OS. The anti-angiogenic activity of C5OSEW5050ESA OS was explored by evaluating its activity towards a variety of angiogenesis modulators in vitro and in vivo. Multiplex immunoassays reveals that C5OSEW5050ESA OS inhibits Vascular Endothelial Growth factor (VEGF), Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF), Interleukin 2 ( IL-2) & Interleukin 7 (IL-7), Nerve Growth Factor β (NGF-β) , Transforming Growth Factor -α (TGF-α) and Tumor Necrosis Factor- β (TNF-β). C5OSEW5050ESA OS also caused significant upregulation of interferon α (IFN-α), interferon β (IFN-β), interferon γ (IFN-γ) and Granulocyte-macrophage colony-stimulating factor (GM-CSF). C5OSEW5050ESA OS was found to inhibit endothelial cell proliferation and migration (92.6%) and disrupts the tube assembly (98.26%) for new blood vessel formation. The compound also inhibits neovascularisation in isolated rat aortic ring tissues (IC50 18.2 ± 2 µg/mL) and in chick chorioallantoic membrane assays (CAM) by 82.7%. In vivo matrigel plug assay treated with C5OSEW5050ESA OS shows inhibition of neovascularisation by 91.4± 3%. In conclusion, the study reveals that C5OSEW5050ESA OS has strong anti-angiogenic and immunomodulatory properties which may have significant clinical benefits in cancer therapy.

Benzimidazolium salts (3−6) were synthesized as stable N-Heterocyclic Carbene (NHC) precursors and their selenium-NHC compounds/Selenones (7−10) were prepared using water as a solvent. Characterization of each of the synthesized compounds was carried out by various analytical and spectroscopic (FT-IR, 1H-, 13C NMR) methods. X-ray crystallographic analyses of single crystals obtained for salts 3 and 5 were carried out. Synthesized salts and their Se-NHCs were tested in-vitro for their anticancer potential against Cervical Cancer Cell line from Henrietta Lacks (HeLa), Breast cancer cell line (MDA-MB-231), Adenocarcinoma cell line (A549) and human normal endothelial cell line (EA.hy926). MTT assay was used for analysis and compared with standard drug 5-flourouracil. Benzimidazolium salts (3−6) and their selenium counter parts (7−10) were found potent anticancer agents. Salt 3–5 were found to be potent anticancer against HeLa with IC50 values 0.072, 0.017 and 0.241 μM, respectively, which are less than standard drug (4.9 μM). The Se-NHCs (7–10) had also shown significant anticancer potential against HeLa with IC50 values less than standard drug. Salts 3, 4 against EA.hy926, compounds 3,5,6, and 10 against MDA-MB-321, and compounds 4, 10 against A-549 cell line were found more potent anticancer agents with IC50 values less than standard drug. Molecular docking for (7−10) showed their good anti-angiogenic potential having low binding energy and significant inhibition constant values with VEGFA (vascular endothelial growth factor), EGF (human epidermal growth factor), COX1 (cyclooxygenase-1) and HIF (hypoxia inducible factor).

The present study was designed to investigate the underlying mechanism of cytotoxic and pro-apoptotic potential of ethyl-p-methoxycinnamate (EPMC) and its hydrophilic derivative potassium-p-methoxycinnamate (KPMC). EPMC was isolated from Kaempferia galanga extract and its ethyl chain was replaced with potassium by KOH reflux to synthesize KPMC. The anti-proliferative effect of EPMC and KPMC was evaluated in six cancer cell lines and two normal cell lines by MTT assay. The inhibitory effects of the test compounds on colony formation, cell migration, chromatin condensation and mitochondrial membrane potential was further investigated in HCT-116 cells whereas their effect on caspase 3, 7, 8 and 9 activities was studied in HCT-116 and PC-3 cells. EPMC exhibited significant antiproliferative effect in all six cancer cell lines with maximum cytotoxicity against HCT-116 cells (selectivity index > 6). Our results showed significant inhibition of cell migration and colony formation in EPMC-treated colorectal carcinoma cells (HCT-116) when compared to the normal colon fibroblasts (CCD-18co). It exhibited dose dependent chromatin condensation and loss of mitochondrial membrane potential with subsequent induction of caspase 3/7 activity. KPMC did not inhibit the proliferation of either cell lines in MTT assay. Moreover, the cell migration, colony formation and caspase induction in KPMC-treated cells was comparable with the negative control. The replacement of alkyl chain in EPMC by potassium resulted into the loss of cytotoxic and pro-apoptotic effects of EPMC.

Four heterocyclic embedded Schiff base derivatives (1–4) were synthesized and characterized by melting point, elemental analysis, FTIR, 1H, 13C NMR, UV–Visible spectral data. The structures of compounds 1, 2 and 4 were successfully established through single crystal X-ray diffraction analysis. In vitro cholinesterase inhibition assays showed that the cyclized derivative 1 displayed higher BuChE enzyme inhibitory activity with IC50 value of 1.45 ± 0.09 μM. The anti-proliferative efficacies of the compounds were also evaluated using human colorectal HCT 116 and breast MCF-7 adenocarcinoma cell lines. In addition, a human normal endothelial cell line (Ea.hy926) was also tested to assess the safety and selectivity of the compounds towards normal and cancer cells, respectively. Among the compounds tested, compound 2 displayed potent cytotoxic effect (IC50 = 34 μM) against HCT 116 cells with highest selectivity index of 3.1 with respect to the normal endothelial cells. Whereas, compound 4 exhibited significant anti-proliferative effect (IC50 = 21.1 μM) against MCF-7 cells with highest selectivity index of 3.3 with respect to the normal endothelial cells. The docking result of these compounds against hAChE showed potent activities with different binding modes. These compounds could be a promising pharmacological agent to treat cancer and Alzheimer's disease.

Present study involves the synthesis and characterization of a newly designed tetrakis benzimidazolium salts, 1–5 and their respective tetra N-heterocyclic carbene (NHC) dinuclear silver(I) complexes, 6–10 with different terminal substituents that constructed from either cyclopentyl, benzyl, n-butyl, 2-methylene benzonitrile or n-decyl. These well characterized compounds were then tested for anticancer potential by determining their IC50 values and antiproliferative activity on HCT116, MCF-7 and HeLa cancer cell lines. Anticancer potential of these compounds was then determined by evaluating the mode of cytotoxicity of these novel compounds. Among the synthesized compounds, the proligand 5 and silver(I)-NHC complex, 10 having n-decyl substitution show selective antiproliferation activity against human colon cancer cell lines (HCT-116). All the complexes 6–10 and proligand 5 show moderate and strong antiproliferative activity against breast cancer and cervical cancer possibly by inhibiting colony formation and migration of cancer cells.

Considering the great potential of natural products as anticancer agents, the present study was designed to explore the molecular mechanisms responsible for anticancer activities of Mesua ferrea stem bark extract against human colorectal carcinoma. Based on MTT assay results, bioactive sub-fraction (SF-3) was selected for further studies using HCT 116 cells. Repeated column chromatography resulted in isolation of less active α-amyrin from SF-3, which was identified and characterized by GC-MS and HPLC methods. α-amyrin and betulinic acid contents of SF-3 were measured by HPLC methods. Fluorescent assays revealed characteristic apoptotic features, including cell shrinkage, nuclear condensation, and marked decrease in mitochondrial membrane potential in SF-3 treated cells. In addition, increased levels of caspases-9 and -3/7 levels were also observed in SF-3 treated cells. SF-3 showed promising antimetastatic properties in multiple in vitro assays. Multi-pathway analysis revealed significant down-regulation of WNT, HIF-1α, and EGFR with simultaneous up-regulation of p53, Myc/Max, and TGF-β signalling pathways in SF-3 treated cells. In addition, promising growth inhibitory effects were observed in SF-3 treated HCT 116 tumour spheroids, which give a hint about in vivo antitumor efficacy of SF-3 phytoconstituents. In conclusion, these results demonstrated that anticancer effects of SF-3 towards colon cancer are through modulation of multiple molecular pathways.

A carbothioamide NSO tridentate Schiff base ligand (HL) and its square planar complexes Na[NiLOAc], Na[PdLOAc] and [PtLdmso] have been synthesized and characterized on the basis of melting point, elemental analysis, FT-IR, 1H NMR, 13C NMR, UV–Vis spectra. The structure of HL was elucidated with X-ray diffraction analysis. In the present study, the synthesized compounds were evaluated for their anticancer properties against three human cancer cell lines breast cancer (MCF-7), cervical (Hela), and colon (HCT-116). In addition, the cytotoxicity of the synthesized compounds was tested on a normal human cell line (human endothelial cell line EA.hy926). Among the tested compounds, the complex [NiLOAc] excelled in halting proliferation of the cervical and colon cancer cells with median inhibitory concentration (IC50) values of 28.33 and 34.4 μM, respectively. The complex, [PdLOAc] demonstrated selective cytotoxicity against breast cancer line MCF-7 with IC50 = 47.5 μM, while HL showed inhibitory effect against colon cancer cell line (HCT-116) with IC50 = 55.66 μM. The complex, [PtLdmso] showed mild activity against breast cancer (MCF-7) and cervical cancer (Hela) cells with IC50 = 64.44 and 68.3 μM, respectively, whereas, it displayed insignificant cytotoxicity against human endothelial cells (EA.hy926) with IC50 > 200 μM. Cancer cells treated with [NiLOAc] showed apoptotic features such as membrane blebbing and DNA condensation. Thus, the findings of the present study demonstrated that the series of metal complexes of HL could form the new lead for development of cancer chemotherapies to treat human cervical, breast and colon malignancies.

Three benzimidazolium salts (III-V) and respective selenium adducts (VI-VIII) were designed, synthesized and characterized by various analytical techniques (FT-IR and NMR 1H, 13C). Selected salts and respective selenium N-Heterocyclic carbenes (selenium-NHC) adducts were tested in vitro against Cervical Cancer Cell line (Hela), Breast Adenocarcinoma cell line (MCF-7), Retinal Ganglion Cell line (RGC-5) and Mouse Melanoma Cell line (B16F10) using MTT assay and the results were compared with standard drug 5-Fluorouracil. Se-NHC compounds and azolium salts showed significant anticancer potential. Molecular docking studies of compounds (VI, VII and VIII) showed strong binding energies and ligand affinity toward following angiogenic factors: VEGF-A (vascular endothelial growth factor A), EGF (human epidermal growth factor), HIF (Hypoxia-inducible factor) and COX-1 (Cyclooxygenase-1) suggesting that the anticancer activity of adducts (VI, VII and VIII) may be due to their strong anti-angiogenic effect. In addition, compounds III-VIII were screened for their antibacterial and antifungal potential. Adduct VI was found to be potent anti-fungal agent against A. Niger with zone of inhibition (ZI) value 27.01 ± 0.251 mm which is better than standard drug Clotrimazole tested in parallel.

N–heterocyclic carbene (NHC) complexes of palladium(II) are generally active as catalysts toward various coupling reactions, while their pharmacological efficiencies are seldom explored. A new series of palladium(II) complexes of both, functionalized and non–functionalized NHCs that were active against the human colon cancer (HCT116) cells are reported. Complexes were prepared by the technique of transmetallation using palladium source and in situ prepared silver(I)–NHC complexes in acetonitrile, and all complexes are characterized using spectroscopic and analytical tools. Additionally, the structure of palladium complex 9 was elucidated using single crystal X–ray diffraction method. In vitro anticancer studies revealed that the palladium complexes, 9 and 10, having xylyl–spacers significantly inhibited the HCT116 cell growth, exhibiting IC50 values in low micromolar range in MTT assay.

The benzimidazolium salt 1, with butyl and allyl substituents, demonstrated two types of coordination behavior with the silver(I) center, in which the bis-NHC complex 2 was formed at room temperature, while the mono-NHC complex 3 was formed at an elevated temperature. However, the reaction of analogous salts with silver(I) oxide under the same reaction conditions did not result in the formation of mono-NHC complexes, instead bis-NHC complexes were formed. A series of palladium(II)-NHC complexes, 4, 5, 10 and 11, were obtained by the treatment of the corresponding silver complexes with a palladium(II) source. All new compounds were characterized by various spectroscopic and analytical techniques. Additionally, the structure of the mono-NHC silver complex 3 was unambiguously established following single crystal X-ray diffraction method. The in vitro comparative evaluation of the salt 1, and the silver complexes 2 and 3, and all the palladium complexes for their anticancer properties against human colon cancer cells indicated that the silver complexes 2 and 3 and palladium complexes 10 and 11 were the most effective antiproliferative compounds and were found able to promote a growth inhibitory effect with IC50 values in the range 10.6 ± 1.8–21.4 ± 2.1 μM.

The proligands of the series tetramethylenebis(N-n-alkylbenzimidazolium bromide) (where n = 3–10) (1–8) as N-heterocyclic carbene (NHC) precursors have been prepared by reacting the initially synthesized N-n-alkyl benzimidazole with 1,4-dibromobutane in 2 : 1 M ratio. A reaction of Ag2O with 1–8 resulted in the formation of Ag(I) complexes tetramethylenebis{(N-n-alkylylbenzimidazol-2-ylidene)silver(I)hexafluorophosphate} (9–16), respectively. All the synthesized compounds were characterized by FT-IR, 1H NMR, 13C NMR, atomic absorption and elemental analysis. Single-crystal X-ray diffraction study on tetramethylenebis{(N-n-octylbenzimidazol-2-ylidene)silver(I)hexafluorophosphate} (14) has revealed that the complex exists as a dinuclear compound. All compounds were assessed for their antiproliferation test on human colorectal cancer cell line (HCT 116). Interestingly, increasing the n-alkyl chain length from n = 3 to 10 of the proligands and their respective complexes showed trends in increased cyto...

We recently reported the antineovascularization effect of scopoletin on rat aorta and identified its potential anti-angiogenic activity. Scopoletin could be useful as a systemic chemotherapeutic agent against angiogenesis-dependent malignancies if its antitumorigenic activity is investigated and scientifically proven using a suitable human tumor xenograft model. In the present study, bioassay-guided (anti-angiogenesis) phytochemical investigation was conducted on Nicotiana glauca extract which led to the isolation of scopoletin. Further, anti-angiogenic activity of scopoletin was characterized using ex vivo, in vivo and in silico angiogenesis models. Finally, the antitumorigenic efficacy of scopoletin was studied in human colorectal tumor xenograft model using athymic nude mice. For the first time, an in vivo anticancer activity of scopoletin was reported and characterized using xenograft models. Scopoletin caused significant suppression of sprouting of microvessels in rat aortic explants with IC50 (median inhibitory concentration) 0.06μM. Scopoletin (100 and 200mg/kg) strongly inhibited (59.72 and 89.4%, respectively) vascularization in matrigel plugs implanted in nude mice. In the tumor xenograft model, scopoletin showed remarkable inhibition on tumor growth (34.2 and 94.7% at 100 and 200mg/kg, respectively). Tumor histology revealed drastic reduction of the extent of vascularization. Further, immunostaining of CD31 and NG2 receptors in the histological sections confirmed the antivascular effect of scopoletin in tumor vasculature. In computer modeling, scopoletin showed strong ligand affinity and binding energies toward the following angiogenic factors: protein kinase (ERK1), vascular endothelial growth factor A (VEGF-A), and fibroblast growth factor 2 (FGF-2). These results suggest that the antitumor activity of scopoletin may be due to its strong anti-angiogenic effect, which may be mediated by its effective inhibition of ERK1, VEGF-A, and FGF-2.

Clinacanthus nutans (CN) is used traditionally for treating various illnesses. Robust safety data to support its use is lacking.To evaluate the adverse effects of aqueous extract of CN leaves (AECNL).The oral toxicity of the AECNL was tested following Organisation for Economic Co-operation and Development (OECD) guidelines. Mutagenicity (Ames test) of AECNL was evaluated using TA98 and TA100 Salmonella typhimurium strains.No mortality or morbidity was found in the animals upon single and repeated dose administration. However, significant body weight loss was observed at 2000 mg/kg during sub-chronic (90 d) exposure. In addition, increased eosinophil at 500 mg/kg and decreased serum alkaline phosphatase levels at 2000 mg/kg were observed in male rats. Variations in glucose and lipid profiles in treated groups were also observed compared to control. Ames test revealed no evidence of mutagenic or carcinogenic effects at 500 μg/well of AECNL.The median lethal dose (LD50) of the AECNL is5000 mg/kg and the no-observed-adverse-effect level is identified to be greater than 2000 mg/kg/day in 90-d study.

This study investigated the antioxidant and in vitro cytotoxic effects of essential oils (EOs) obtained from the fruits of Illicium verum. The solvent extraction method was used to extract oils from the fruits. Antioxidant properties were assessed using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and ferric reducing antioxidant power (FRAP) assays followed by estimation of the total phenolic and total flavonoid contents and gas chromatography–mass spectrometry (GC-MS) analysis. Anti-proliferative effects were studied by MTT assay. Fluorescent dyes were used to study the apoptotic effects of EOs. Furthermore, in vitro cell migration, matrigel invasion, and colony formation assays were employed to study the anti-metastatic properties of EOs. Three concentrations of EOs (25, 50, and 90 μg/mL), 0.5% dimethyl sulfoxide in media, and 5-Fluorouracil (5 μg/mL) were used as the test sample, negative control, and positive control, respectively. EOs showed promising antioxidant effects in the DPPH and FRAP models; GC-MS analysis identified trans-anethole as one of the major compounds. Among the cell lines tested, EOs showed the greatest cytotoxicity towards HCT 116, with an IC50 value of 50.34 ± 1.19 μg/mL. Distinct nuclear morphological changes and a reduction in mitochondrial membrane potential was observed in the treated cells in a dose-dependent manner. Similarly, dose-dependent inhibition of cell migration, invasion, and colony formation was observed in the treated cells. To conclude, the cytotoxic effect of Illicium verum EOs may be due to multiple mechanisms such as the induction of apoptosis and inhibition of key steps of metastasis.

Synthesis of ethylene linked tris benzimidazolium bromide salts that serve as precursors for the tri-NHC ligands in the respective tri-NHC trinuclear silver(I) complexes is described (NHC = N-heterocyclic carbene). Different wingtip substituents were selected (benzyl, n-butyl, cyclopentyl, 2-methylene benzonitrile, n-decyl) to furnish five new tris benzimidazolium salts (1-5) and the respective tri-NHC trinuclear silver(I) complexes (6-10). The synthesized and characterized compounds (1-10) were evaluated for their cytotoxic potential on human colon, human breast and human epitheloid cervix cancer cell lines by determining their IC50 values and evaluating their antiproliferative activity against the selected cell lines. The tested compounds were found to be good anticancer agents against breast cancer and cervical cancer cell lines and selectively good anticancer agents for the human colon cancer cell line.

Purpose Koetjapic acid is an active compound of a traditional medicinal plant, Sandoricum koetjape. Although koetjapic acid has a promising anticancer potential, yet it is highly insoluble in aqueous solutions. To increase aqueous solubility of koetjapic acid, we have previously reported a chemical modification of koetjapic acid to potassium koetjapate (KKA). However, pharmacokinetics of KKA has not been studied. In this study, pharmacokinetics and antiangiogenic efficacy of KKA are investigated. Methods Pharmacokinetics of KKA was studied after intravenous and oral administration in SD rats using HPLC. Anti-angiogenic efficacy of KKA was investigated in rat aorta, human endothelial cells (EA.hy926) and nude mice implanted with matrigel. Results Pharmacokinetic study revealed that KKA was readily absorbed into blood and stayed for a long time in the body with Tmax 2.89 ± 0.12 h, Cmax 7.24 ± 0.36 μg/mL and T1/2 1.46 ± 0.03 h. The pharmacological results showed that KKA significantly suppressed sprouting of microvessels in rat aorta with IC50 18.4 ± 4.2 μM and demonstrated remarkable inhibition of major endothelial functions such as migration, differentiation and VEGF expression in endothelial cells. Further, KKA significantly inhibited vascularization in matrigel plugs implanted in nude mice. Conclusions The results indicate that bioabsorption of KKA from oral route was considerably efficient with longer retention in body than compared to that of the intravenous route. Further, improved antiangiogenic activity of KKA was recorded which could probably be due to its increased solubility and bioavailability. The results revealed that KKA inhibits angiogenesis by suppressing endothelial functions and expression of VEGF.

After the publication of this article [1] it came to our attention that one author, Boon Yin Khoo, was erroneously omitted from the authorship list.

Modulating oxidative stresses and inflammation can potentially prevent or alleviate the pathological conditions of diseases associated with the nervous system, including ischemic optic neuropathy. In this study we evaluated the anti-neuroinflammatory and neuroprotective activities of Rhus coriaria (R. coriaria) extract in vivo. The half maximal inhibitory concentration (IC50) for DPPH, ABTS and β–carotene were 6.79 ± 0.009 µg/mL, 10.94 ± 0.09 µg/mL, and 6.25 ± 0.06 µg/mL, respectively. Retinal ischemia was induced by optic nerve crush injury in albino Balb/c mice. The anti-inflammatory activity of ethanolic extract of R. coriaria (ERC) and linoleic acid (LA) on ocular ischemia was monitored using Fluorescence Molecular Tomography (FMT). Following optic nerve crush injury, the mice treated with 400 mg/kg of ERC and LA exhibited an 84.87% and 86.71% reduction of fluorescent signal (cathepsin activity) respectively. The results of this study provide strong scientific evidence for the neuroprotective activity of the ERC, identifying LA as one of the main components responsible for the effect. ERC may be useful and worthy of further development for its adjunctive utilization in the treatment of optic neuropathy.

A series of cationic, linearly coordinated silver(I)– (4–6) and gold(I)/(III)–NHC (NHC = N-heterocyclic carbene) (7–9) complexes of (benz)imidazol-2-ylidene ligands was prepared and successfully characterized. Complexes 4–6 were prepared by in situ deprotonation of azolium salts and 7–9 by NHC transfer from their respective silver(I) complexes. All new compounds were characterized by elemental analysis and 1H, 13C NMR, and FTIR spectroscopy techniques, and four of the complexes were unambiguously characterized by single-crystal X-ray diffraction method. Results of structural studies on single crystals of 5a, 6, and 8 revealed a linear coordination geometry about the metal center, whereas gold(III) in complex 7 had a consistent square-planar geometry. The reaction of complex 4 with gold(I) source formed a gold(III)–NHC complex following redox transmetallation. In all these cases, metal⋯H and π⋯π stacking interactions were observed, which affected the Ccarbene–M–Ccarbene bond angle. Preliminary anticancer activities of all new compounds were also studied in vitro against four human derived cancer cell lines by MTT assay method. Cationic silver(I) complexes displayed better anticancer potentials than their gold(I) counterparts. In particular, gold(III) complex displayed superior activity, with IC50 values at low-micro and nanomolar levels; thus, this complex showed superior selectivity toward all four tested cancer cell lines.

Two new series of aurone compounds were synthesized via an oxidative cyclization reaction of 2′-hydroxy-chalcones. Series (A) consists of 1a–3a aurones with different substitutions on a B-ring at position 4′, and series (B) is made up of 1b–3b aurones that have different substitutions at position 2′ of a B-ring. Structures of the synthesized compounds were characterized and confirmed by FTIR (1D and 2D NMR) and EI mass spectral studies. The molecular structure of 2b was further confirmed by the X-ray crystallographic technique, with the compound found to be in Z-isomeric form. The compounds of both series were tested for their antiproliferative activity against human colorectal tumor (HCT 116), human chronic myelogenous leukemia (K562) and hormone-dependent breast cancer (MCF-7) cell lines according to an MTT assay. Series (B) exhibited a higher cytotoxic effect on the cancer cell lines compared to series (A). Selectively, the most promising results have been shown by the two most active compounds, 1b (Z-5,7, 2′-trichloro-aurone), which resulted in IC50 values of 36, 23 and 23 μM against HCT 116, MCF-7 and K562 cancer cells, respectively. Compound 3a (Z-5, 7-dichloro-4′-methyl-aurone) exhibited the highest activity against the K562 cell line (IC50 = 20 μM), which can be compared to that of the standard drug, betulinic acid, with an IC50 value of 15 μM. The results of the present study suggested that aurone derivatives emerged as a potential candidate for the development of future chemotherapeutic agents.

The synthesis of a series of silver(I) complexes (3a–d), [1-(2′/3′-methylbenzyl)-3-(2″/3″-benzonitrile)benzimidazol-2-ylidenesilver(I)]PF6, of nitrile-functionalized N-heterocyclic carbenes (NHCs) based on benzimidazole core and their characterization and biological evaluations have been reported. The NHC precursors (1a–d and 2a–d) have been synthesized from successive N-alkylation of benzimidazole with appropriate substituted benzyl halides. Their corresponding bis-NHC silver(I) complexes, 3a–d, have been prepared from the reaction of the nitrile-functionalized benzimidazolium salts with silver(I) oxide in methanol/acetonitrile at mild reaction conditions in good yield (65–73%). Both, salts and complexes, were characterized by 1H and 13C NMR, FT-IR spectroscopic and elemental analysis techniques. The molecular structures of the silver(I)–NHC complexes, 3a and 3c, were elucidated by X-ray diffraction technique. Both the complexes displayed weak π–π stacking interactions between benzimidazole and benzyl benzene rings. All four silver(I) complexes exhibited potent antimicrobial activity against a Gram negative (Escherichia coli) and Gram positive (Staphylococcus aureus and Bacillus subtilis) bacteria. Also the IC50 values of both, salts (2a–d) and complexes (3a–d) have been determined by an MTT-based assay method against the human colon cancer cell line, HCT 116. Complexes 3a–d displayed three- to fivefold increase in the anticancer activity with the IC50 values 18.8 ± 1.3, 20.6 ± 1.5, 19.2 ± 1.0, 14.9 ± 0.8 μM compared to the anticancer potential of salts 2a–d (64.3 ± 2.5, 58.3 ± 4.5, 83.9 ± 1.5, 72.4 ± 1.0 μM), respectively.

The present study reports a bioassay-guided isolation of β-caryophyllene from the essential oil of Aquilaria crassna. The structure of β-caryophyllene was confirmed using FT-IR, NMR and MS. The antimicrobial effect of β-caryophyllene was examined using human pathogenic bacterial and fungal strains. Its anti-oxidant properties were evaluated by DPPH and FRAP scavenging assays. The cytotoxicity of β-caryophyllene was tested against seven human cancer cell lines. The corresponding selectivity index was determined by testing its cytotoxicity on normal cells. The effects of β-caryophyllene were studied on a series of in vitro antitumor-promoting assays using colon cancer cells. Results showed that β-caryophyllene demonstrated selective antibacterial activity against S. aureus (MIC 3 ± 1.0 µM) and more pronounced anti-fungal activity than kanamycin. β-Caryophyllene also displayed strong antioxidant effects. Additionally, β-caryophyllene exhibited selective anti-proliferative effects against colorectal cancer cells (IC50 19 µM). The results also showed that β-caryophyllene induces apoptosis via nuclear condensation and fragmentation pathways including disruption of mitochondrial membrane potential. Further, β-caryophyllene demonstrated potent inhibition against clonogenicity, migration, invasion and spheroid formation in colon cancer cells. These results prompt us to state that β-caryophyllene is the active principle responsible for the selective anticancer and antimicrobial activities of A. crassnia. β-Caryophyllene has great potential to be further developed as a promising chemotherapeutic agent against colorectal malignancies.

Chronic inflammation intensifies the risk for malignant neoplasm, indicating that curbing inflammation could be a valid strategy to prevent or cure cancer. Cancer and inflammation are inter-related diseases and many anti-inflammatory agents are also used in chemotherapy. Earlier, we have reported a series of novel ligands and respective binuclear Ag(I)–NHC complexes (NHC = N -heterocyclic carbene) with potential anticancer activity. In the present study, a newly synthesized salt ( II ) and respective Ag(I)–NHC complex ( III ) of comparable molecular framework were prepared for a further detailed study. Preliminarily, II and III were screened against HCT-116 and PC-3 cells, wherein III showed better results than II . Both the compounds showed negligible toxicity against normal CCD-18Co cells. In FAM-FLICA caspase assay, III remarkably induced caspase-3/7 in HCT-116 cells most probably by tumor necrosis factor-alpha (TNF-α) independent intrinsic pathway and significantly inhibited in vitro synthesis of cytokines, interleukin-1 (IL-1) and TNF-α in human macrophages (U937 cells). In a cell-free system, both the compounds inhibited cyclooxygenase (COX) activities, with III being more selective towards COX-2. The results revealed that III has strong antiproliferative property selectively against colorectal tumor cells which could be attributed to its pro-apoptotic and anti-inflammatory abilities.

Cancer has become a leading cause of death worldwide, which is responsible for 7.6 million cancer deaths according to GLOBOCAN survey conducted in 2008. The exploration of cis -platin analogues (carboplatin, lobaplatin, nedaplatin, oxaliplatin) and their incorporation to the treatment of cancer patients has further led interest in exploring metal-based anticancer drugs. The current study describes the synthesis of two new tetra-coordinated mono- and tetranuclear organotin(IV) carboxylate complexes and their in vitro anticancer studies. Each one of the complexes ( 1–2 ) has been characterized by analytical (micro- and gravimetric analysis) and spectroscopic (FTIR, 1 H, 13 C, 119 Sn-NMR) techniques. Furthermore, molecular structures of 1 and 2 were elucidated using X-ray crystallography. The characterization data showed that the coordination took place via oxygen atoms from the carboxylate anions to generate 1 as an organodistannoxane dimer and 2 as a mononuclear complex. Exceptionally, the NMR spectroscopic and X-ray crystallographic study showed that acetone molecules also took part in crystallizing 2 . Both complexes were tested against three cancerous (colon cancer HCT 116, breast cancer MCF 7, leukemia K562) and one non-cancerous (3T3-L1) cell lines. Both complexes showed same IC 50 value (0.2 μM) against HCT 116, whereas for the other two cancer cell lines (MCF 7 and K562) and a normal cell line (3T3-L 1 ), 2 showed results better than 1 . Importantly, the complexes showed exceptional activity against MCF 7 and K562 cell lines and the IC 50 values were calculated in nanomoles (MCF 7, IC 50s = 86.5 and 53.4 nM; K 562, IC 50s = 22.9 and 49.6 nM for 1 and 2 , respectively). Both, 1 and 2 , showed IC 50 values many times better than the standard drugs (5-FU, Tamoxifen, betulinic acid and cis -platin) used. Compared to cancerous cell lines, the complexes showed mild toxicity against normal cells (3T3-L1). Overall, two remained relatively effective.

Four dioxomolybdenum(VI) complexes were synthesized by reacting [MoO2(acac)2] with N-ethyl-2-(5-bromo-2-hydroxybenzylidene) hydrazinecarbothioamide (1), N-ethyl-2-(5-allyl-3-methoxy-2-hydroxybenzylidene) hydrazinecarbothioamide (2), N-methyl-2-(3-tert-butyl-2-hydroxybenzylidene) hydrazinecarbothioamide (3), and N-ethyl-2-(3-methyl-2-hydroxybenzylidene) hydrazinecarbothioamide (4). The molecular structures of 1, 2, and all the synthesized complexes were determined using single crystal X-ray crystallography. The binding properties of the ligand and complexes with calf thymus DNA (CT-DNA) were investigated via UV, fluorescence titrations, and viscosity measurement. Gel electrophoresis revealed that all the complexes cleave pBR 322 plasmid DNA. The cytotoxicity of the complexes were studied against the HCT 116 human colorectal cell line. All the complexes exhibited more pronounced activity than the standard reference drug 5-fluorouracil (IC50 7.3 μM). These studies show that dioxomolybdenum(VI) complexes could be potentially useful in chemotherapy.

Four dioxomolybdenum(VI) complexes were synthesized by the reaction of [MoO2(acac)2] with thiosemicarbazone ligands derived from 5-chloro-2-hydroxy-benzaldehyde (1), 2-hydroxy-5-methoxybenzaldehyde (2), 2-hydroxy-5-methylbenzaldehyde (3), or 5-tert-butyl-2-hydroxybenzaldehyde (4). In all complexes, the ligands were coordinated to molybdenum as tridentate ONS donors. X-ray crystallography results show that the distorted octahedral coordination of the molybdenum atom is completed by a methanol molecule (D), as in 1a, 3a, and 4a, or by H2O, as in 4a. The molecular structures of 1, 2, and the complexes were determined by single-crystal X-ray crystallography. The binding properties of the ligand and complexes with calf thymus DNA (CT DNA) were investigated by UV titration, fluorescence titration, and viscosity measurements. Gel electrophoresis assay results show that the complexes can cleave the pBR 322 plasmid DNA. The cytotoxic activities of the complexes were investigated against human colorectal cell lines. All complexes showed high anticancer activities in the order, 4a > 1a ≫ 3a > 2a, according to their IC50 values (3.4, 3.5, 6.4, and 6.9 μM, respectively).

Four dioxomolybdenum(VI) complexes were synthesized by reacting [MoO2(acac)2] with thiosemicarbazone ligands derived from 5-chloro-2-hydroxybenzaldehyde (H2L1), 2-hydroxy-5-methylbenzaldehyde (H2L2), 3-tert-butyl-2-hydroxybenzaldehyde (H2L3), or 2,3-dihydroxybenzaldehyde (H2L4). In all the complexes, the ligands were coordinated to molybdenum as tridentate ONS donors. X-ray crystallography showed that the distorted octahedral coordination of molybdenum atom is completed by methanol molecule (D) as in [MoO2(L1D)], [MoO2(L2D)], and [MoO2(L3D)], or by an ethanol molecule as in [MoO2(L4D)]. The molecular structures of H2L2, H2L3, and all synthesized complexes were determined via single crystal X-ray crystallography. The binding properties of the ligand and the complexes with calf thymus DNA were analyzed by UV, fluorescence titration, and viscosity measurements. Gel electrophoresis shows that all complexes can cleave the pBR322 plasmid DNA. The cytotoxic properties of the complexes were studied against human colorectal cell lines. All complexes showed strong antiproliferative activities in the relative order [MoO2(L3D)] > [MoO2(L1D)] ∼ [MoO2(L2D)] > [MoO2(L4D)] with IC50 values of 3.2, 4.5, 4.6, and 6.4 μM, respectively. The complexes exhibited greater pronounced activity than the standard reference drug, 5-fluorouracil, did (IC50 = 7.3 μM). These studies demonstrate the potential application of dioxomolybdenum(VI) complexes in chemotherapy.

Objectives Recently, we have isolated koetjapic acid (KA) from Sandoricum koetjape and identified its selective anticancer potentiality against colorectal carcinoma. KA is quite likely to be useful as a systemic anticancer agent against colorectal malignancy. However, with extremely low solubility, KA has to be converted into a biocompatible solubilized form without compromising the bioefficacy. Objective of this study is to enhance solubility of KA and to evaluate anticancer efficacy of potassium koetjapate in human colorectal cancer cells. Methods (2-Hydroxypropyl)-β-cyclodextrin inclusion complex and solid dispersions (carboxymethyl cellulose, polyvinylpyrrolidone and sodium lauryl sulphate) of KA were prepared. In addition, a salt of KA, potassium koetjapate was synthesized. Key findings Potassium koetjapate demonstrated higher solubility than the other tested formulations with enhanced cytotoxicity against HCT 116 cells. The enhanced efficacy of potassium koetjapate is attributed to apoptotic induction of nuclear condensation and disruption of mitochondrial membrane potential in the cells. Interestingly, potassium koetjapate was found to be safe in rats after oral administration (LD50 > 2000 mg/kg). Conclusions The salt formulation of KA appears to modulate the capability of the parent compound by enhancing its solubility and improves its bioefficacy against colon cancer cells, suggesting attractive roles for its applications in medicine.

New derivatives of thiosemicarbazone Schiff base with isatin moiety were synthesized L1-L6. The structures of these compounds were characterized based on the spectroscopic techniques. Compound L6 was further characterized by XRD single crystal. The interaction of these compounds with calf thymus (CT-DNA) exhibited high intrinsic binding constant (k(b)=5.03-33.00×10(5) M(-1)) for L1-L3 and L5 and (6.14-9.47×10(4) M(-1)) for L4 and L6 which reflect intercalative activity of these compounds toward CT-DNA. This result was also confirmed by the viscosity data. The electrophoresis studies reveal the higher cleavage activity of L1-L3 than L4-L6. The in vitro anti-proliferative activity of these compounds against human colon cancer cell line (HCT 116) revealed that the synthesized compounds (L3, L6 and L2) exhibited good anticancer potency.

Six new platinum(II) complexes of a thiosemicarbazone Schiff base with isatin moiety [PtL1 to Pt(L6)2] were synthesized by the reaction of platinum(II) with the following: (Z)-2-(2-oxoindolin-3-ylidene)-N-phenylhydrazinecarbothioamide [L1H], (Z)-2-(5-methyl-2-oxoindolin-3-ylidene)-N-phenylhydrazinecarbothioamide [L2H], (Z)-2-(5-fluoro-2-oxoindolin-3-ylidene)-N-phenylhydrazinecarbothioamide [L3H], (Z)-N-methyl-2-(5-nitro-2-oxoindolin-3-ylidene)hydrazinecarbothioamide [L4H], (Z)-N-methyl-2-(5-methyl-2-oxoindolin-3-ylidene)hydrazinecarbothioamide [L5H], and (Z)-N-ethyl-2-(5-methyl-2-oxoindolin-3-ylidene)hydrazinecarbothioamide [L6H]. The structures of these complexes were characterized by elemental analysis, IR, UV–Vis, 1H NMR, and mass spectrometry analyses. The structure of Pt(L6)2 was further characterized by single-crystal XRD. The interaction of these complexes with calf thymus (CT) DNA exhibited a high intrinsic binding constant (Kb = 3.5 × 104 to 3.29 × 106 M−1), which reflected the intercalative activity of these complexes toward CT DNA. This result was also confirmed by viscosity data. Data obtained from the in vitro anti-proliferative study clearly established the anticancer potency of PtL1, PtL2, PtL3, PtL5, and Pt(L6)2 against the human colorectal carcinoma cell line HCT 116.

Six new Cu(II) complexes of thiosemicarbazone Schiff base with isatin moiety were synthesized through the reaction of Cu(II) with (Z)-2-(2-oxoindolin-3-ylidene)-N-phenylhydrazinecarbothioamide (CuL1), (Z)-2-(5-methyl-2-oxoindolin-3-ylidene)-N-phenylhydrazinecarbothioamide (CuL2), (Z)-2-(5-fluoro-2-oxoindolin-3-ylidene)-N-phenylhydrazinecarbothioamide (CuL3), (Z)-N-methyl-2-(5-nitro-2-oxoindolin-3-ylidene)hydrazinecarbothioamide (CuL4), (Z)-N-methyl-2-(5-methyl-2-oxoindolin-3-ylidene)hydrazinecarbothioamide (CuL5), and (Z)-N-ethyl-2-(5-methyl-2-oxoindolin-3-ylidene)hydrazinecarbothioamide (CuL6). The structures of the Schiff bases and their copper complexes were characterized based on the elemental analysis, and on the infrared, UV–Vis, 1H and 13C NMR and ESI-mass spectral data. The structures of the CuL2 and CuL3 complexes were further characterized by single-crystal X-ray diffraction. The interaction of these complexes with calf thymus (CT)-DNA exhibited high intrinsic binding constant (Kb = 1.6 × 105–14.6 × 105 M−1), which reflected intercalative activity of these complexes toward CT-DNA. This result was also confirmed by the viscosity data. Electrophoresis studies revealed that the CuL1 and CuL2 complexes were able to cleave the DNA via oxidative pathway, whereas CuL3, CuL4, CuL5, and CuL6 induced DNA cleavage via oxidative and hydrolytic pathways. The in vitro anti-proliferative study establishes the anticancer potency of these compounds against the human colorectal carcinoma cell line.

Four dioxomolybdenum(VI) complexes were synthesized by reaction of [MoO2(acac)2] with thiosemicarbazones derived from 5-allyl-2-hydroxy-3-methoxybenzaldehyde (1), 2-hydroxynaphthaldehyde (2), 2,3-dihydroxybenzaldehyde (3), or 5-tert-butyl-2-hydroxybenzaldehyde (4). The ligands were coordinated to molybdenum as tridentate ONS donors. X-ray crystallography showed that the distorted octahedral coordination of molybdenum is completed by methanol (D) in 1a, 3a, and 4a or H2O in 2a. The molecular structures of 1, 3, and 4, and the complexes were determined by single-crystal X-ray crystallography. Binding of the ligand and complexes with calf thymus DNA were investigated by UV, fluorescence titrations, and viscosity measurements. Gel electrophoresis revealed that all the complexes can cleave pBR322 plasmid DNA. The cytotoxic properties of the complexes against human colorectal (HCT 116) cell line showed strong antiproliferative activities in relative order 4a > 3a > 1a > 2a with IC50 values of 1.6, 4.0, 4.8, and 6.7 μM, respectively. The complexes exhibited more activity than the standard reference drug, 5-fluorouracil (IC50 7.3 μM). These studies show that dioxomolybdenum(VI) complexes have potential use in chemotherapy.

OBJECTIVE: The present study aimed to investigate the mechanisms underlying the anti-inflammatory and anti-angiogenic effects of ethyl-p-methoxycinnamate isolated from Kaempferia galanga. METHODS: The anti-inflammatory effects of ethyl-p-methoxycinnamate were assessed using the cotton pellet granuloma assay in rats, whereby the levels of interleukin-1 and tumor necrosis factor-α were measured in the animals' blood. In addition, the levels of interleukin, tumor necrosis factor, and nitric oxide were measured in vitro using the human macrophage cell line (U937). The analgesic effects of ethyl-p-methoxycinnamate were assessed by the tail flick assay in rats. The anti-angiogenic effects were evaluated first by the rat aortic ring assay and, subsequently, by assessing the inhibitory effects of ethyl-p-methoxycinnamate on vascular endothelial growth factor, proliferation, migration, and tube formation in human umbilical vein endothelial cells. RESULTS: Ethyl-p-methoxycinnamate strongly inhibited granuloma tissue formation in rats. It prolonged the tail flick time in rats by more than two-fold compared with the control animals. The inhibition of interleukin and tumor necrosis factor by ethyl-p-methoxycinnamate was significant in both in vivo and in vitro models; however, only a moderate inhibition of nitric oxide was observed in macrophages. Furthermore, ethyl-p-methoxycinnamate considerably inhibited microvessel sprouting from the rat aorta. These mechanistic studies showed that ethyl-p-methoxycinnamate strongly inhibited the differentiation and migration of endothelial cells, which was further confirmed by the reduced level of vascular endothelial growth factor. CONCLUSION: Ethyl-p-methoxycinnamate exhibits significant anti-inflammatory potential by inhibiting pro-inflammatory cytokines and angiogenesis, thus inhibiting the main functions of endothelial cells. Thus, ethyl-p-methoxycinnamate could be a promising therapeutic agent for the treatment of inflammatory and angiogenesis-related diseases.

Nigella sativa, commonly referred as black cumin, is a popular spice that has been used since the ancient Egyptians. It has traditionally been used for treatment of various human ailments ranging from fever to intestinal disturbances to cancer. This study investigated the apoptotic, antimetastatic, and anticancer activities of supercritical carbon dioxide (SC-CO2) extracts of the seeds of N. sativa Linn. against estrogen-dependent human breast cancer cells (MCF-7). Twelve extracts were prepared from N. sativa seeds using the SC-CO2 extraction method by varying pressure and temperature. Extracts were analyzed using FTIR and UV-Vis spectrometry. Cytotoxicity of the extracts was evaluated on various human cancer and normal cell lines. Of the 12 extracts, 1 extract (A3) that was prepared at 60°C and 2500 psi (~17.24 MPa) showed selective antiproliferative activity against MCF-7 cells with an IC50 of 53.34±2.15 μg/mL. Induction of apoptosis was confirmed by evaluating caspases activities and observing the cells under a scanning electron microscope. In vitro antimetastatic properties of A3 were investigated by colony formation, cell migration, and cell invasion assays. The elevated levels of caspases in A3 treated MCF-7 cells suggest that A3 is proapoptotic. Further nuclear condensation and fragmentation studies confirmed that A3 induces cytotoxicity through the apoptosis pathway. A3 also demonstrated remarkable inhibition in migration and invasion assays of MCF-7 cells at subcytotoxic concentrations. Thus, this study highlights the therapeutic potentials of SC-CO2 extract of N. sativa in targeting breast cancer.

Two ternary copper(II) complexes of dl-threonine and polypyridyl ligands with formula of [Cu(Thr)(Byp)Cl]·H2O (1) and [Cu(Thr)(Phen)H2O]Cl·2H2O (2) were synthesized. The complexes were characterized by spectral (NMR, FT-IR, and UV–Vis), CHN elemental analysis and have been structurally elucidated by X-ray crystallography. Both of the complexes formed slightly distorted square-pyramidal coordination geometry. The electronic absorption spectra of the complexes showed a very low intensity d–d electronic band in the range of 610–620 nm in Tris–HCl/NaCl (5:5 mM) pH 7.2 buffer solution. The DNA binding interaction with calf-thymus DNA (CT-DNA) was investigated by electronic absorption spectral titration and viscosity measurements. The results revealed that the phenanthroline complex (2) interact with CT-DNA through intercalation while bipyridyl complex (1) through the groove binding mode. The calculated intrinsic binding constant (Kb) of (1) and (2) were 0.5 and 4.4 × 105 M−1, respectively. Both the complexes were found to promote efficient DNA cleavage activities at low concentration in the presence of H2O2. The results showed that (2) has the highest DNA binding and nuclease activity. Furthermore, both the complexes were tested against human colon cancer (HCT 116) and breast cancer (MCF-7) cell lines and showed a dose-dependent antiproliferation effect.

The synthesis, spectral (FT-IR and NMR), and structural studies of 1,1′-methylene linked 3,3′-2-cyanobenzyl bis-imidazolium salt (L1) and respective dinuclear Ag(I)-NHC complex (C1) are reported. The structures of both compounds were established through single-crystal X-ray diffraction. C1 has a short Ag–Ag separation of 3.16 A. Both L1 and C1 were tested for potential against leukemia (k562) cell line. For comparison, para-xylyl linked bis-benzimidazolium salts (L2–L4) and their dinuclear Ag(I)-NHC complexes (C2–C4) were synthesized and tested against the same cell line (K562). The IC50 values proved that L2–L4 and C2–C4 are many fold more active than L1 and C1. The mechanism of action and structure activity relationship are discussed. In vivo oral acute toxicity study (sighting study) was carried out which depicts that 2000 mg/kg dose of selected compounds is an appropriate and safe dose for conducting main study on animals.