Further insights into chemical characterization through GC–MS and evaluation for anticancer potential of Dracaena draco leaf and fruit extracts

The present study reports for the first time the amino acid and fatty acid compositions and the antitumoral activity of aqueous extracts obtained from Dracaena draco L. leaf and fruit. Metabolite profiles were determined by gas chromatography-ion trap-mass spectrometry (GC–IT-MS), with several amino acids, palmitic, linolenic and stearic acid being identified in the leaf extract, and only proline, oleic and stearic acid in the fruit extract. The in vitro antiproliferative activities of the extracts were tested against human colon (Caco-2), kidney (A-498), and liver (HepG2) cancer cell lines. In addition, primary cultures of normal and cancerous renal cells derived from kidney cancer patients were treated with D. draco extracts (0–400 μg/mL). Antiproliferative and cytotoxic effects were determined by the MTT assay. D. draco extracts inhibited proliferation of human colon and renal tumor cells in vitro, whereas no or weak effect was observed in HepG2 cells. Compared to the fruit extract, D. draco leaf extract exhibited stronger antiproliferative activity against all cancer cells. Our results indicate that D. draco, particularly the leaf, may be useful as a cancer chemopreventive and/or chemotherapeutic agent for colon and kidney cancers.     

Synthesis and Biological Evaluation of Novel 6‐Hydrazinyl‐2,4‐bismorpholino pyrimidine and 1,3,5‐Triazine Derivatives as Potential Antitumor Agents

A series of 6‐hydrazinyl‐2,4‐bismorpholino pyrimidine and 1,3,5‐triazine derivatives ( 5a – 5l and 8a – 8o ) were synthesized and their chemical structures as well as the relative stereochemistry were confirmed. All the synthesized compounds were evaluated for antiproliferative activity against three cancer cell lines (H460, HT‐29, and MDA‐MB‐231). Several potent compounds were further evaluated against two other cell lines (U87MG, H1975). Most of the prepared compounds, particularly compounds 5c and 5j with IC₅₀ values (0.07 and 0.05 µM, respectively) in the nM range, exhibited moderate to excellent antiproliferative activity and high selectivity against the H460 cancer cell line as compared with compound 1 . The most promising compound 5j , possessing a cyano group at the 3‐position of the benzene ring, showed strong antiproliferative activity against H460, HT‐29, and MDA‐MB‐231 cell lines with IC₅₀ values of 0.05, 6.31, and 6.50 µM, which were 4.6‐ to 190.4‐fold more active than compound 1 (9.52, 29.24, and 36.21 µM), respectively.     

Hyptis verticillata Jacq: A review of its traditional uses,phytochemistry, pharmacology and toxicology

Ethnopharmacological relevance

Hyptis verticillata Jacq. (Lamiaceae) (John Charles) is an important medicinal plant with a long history of traditional use, originating in Central America and now extending from Florida to Colombia and across the Caribbean. Records of its earliest use date back to the ancient Mayan and Aztec cultures of Mesoamerica. There is no indication that this plant is being used outside of the Americas.

Aim of the review

This review aims to provide a comprehensive overview of the traditional use, phytochemistry, pharmacological activity and toxicology of Hyptis verticillata and to highlight the opportunities for greater development of the plant's medicinal properties at a local and international level.

Materials and methods

An extensive and systematic review of the literature was undertaken and all relevant abstracts and full-text articles analysed and included in the review.

Key findings

A wide range of traditional uses are cited in the literature, from internal uses for conditions affecting the respiratory system, digestive tract and gynaecological system to external uses for conditions affecting the skin and musculoskeletal system. Pharmacological studies to date have demonstrated significant activity which support the traditional use of the plant as an antiinflammatory, antimicrobial, antisecretory agent and hormone modulator. In addition studies have identified anti-cancer, acaricidal, insecticidal and molluscicidal activity. No clinical trials had been completed at the time of this review. A number of key phytochemicals have been isolated, identified and published to date including: 17 lignans; 4 triterpenes; 11 diterpenes, 3 sesquiterpenes, 3 monoterpenes, 2 flavonoids, 1 polyphenol and 1 alkaloid. Nine of these phytochemicals are novel to Hyptis verticillata. Plant extracts and isolated phytochemicals exhibit a broad range of activities that include: antimitotic; antiproliferative; cytotoxic; antioxidant; antiinflammatory; antibacterial; antifungal; antiviral; anti-HIV; antisecretory; hepatoprotective; insecticidal and acaricidal.

Conclusions

Hyptis verticillata is a medicinal plant with current widespread traditional use in the Americas that warrants further research, clinical trials and product development to fully exploit its medicinal value.     

New imidazo[2,1-b]thiazole derivatives: synthesis, in vitro anticancer evaluation, and in silico studies

A series of 18 new imidazo[2,1-b]thiazole derivatives was synthesized. Their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-60 cell line panel were tested. Compounds 15, 16, 18, 22, 26–28, and 31 showed superior potency against A375P to sorafenib. In addition, compounds 26 and 27 showed selectivity toward melanoma cell lines than for other cancer types. Both compounds exerted sub-micromolar IC₅₀ values over 7 (including A375P) and 6 melanoma cell lines, respectively. In silico studies are also reported. ADME profiling, in silico toxicity, drug-likeness, and drug-score data of compounds 26 and 27 are promising.     

Total synthesis and bioactivity of the marine alkaloid pityriacitrin and some of its derivatives

We report herein the chemical synthesis and biological evaluation of β-carboline alkaloid pityriacitrin and some of its new derivatives. Using tryptophan or 5-hydroxytryptophan and 5-substituted indole-3-glyoxals as the starting materials, pityriacitrin and some of its derivatives were synthesized via the acid-catalyzed Pictet–Spengler reaction and fully characterized by ¹H and ¹³C NMR, mass spectroscopy and IR determinations. Biological studies revealed that pityriacitrin has a weak antiproliferative activity against a panel of breast and prostate cancer cell lines, whereas some of its derivatives exhibited stronger and potent activity, which was associated with induction of both cell apoptosis and necrosis.     

3-Aryl-2-[1H-benzotriazol-1-yl]acrylonitriles: a novel class of potent tubulin inhibitors

During a screening for compounds that could act against Mycobacterium tuberculosis, a series of new cellular antiproliferative agents was identified. The most cytotoxic molecules were evaluated against a panel of human cell lines derived from hematological and solid human tumors. In particular, (E)-2-(1H-benzo[d] [1,2,3]triazol-1-yl)-3-(4-methoxyphenyl)acrylonitrile (1) was found to be of a potency comparable to etoposide and greater than 6-mercaptopurine in all cell lines tested. Accordingly, a synthesis of a new series of (E)-2-(5,6-dichloro-1H-benzo[d] [1,2,3]triazol-1-yl)-3-(4-R-phenyl)acrylonitriles was conducted in order to extend the studies of structure-activity relationship (SAR) for this class of molecules. With the aim to evaluate if 3-aryl-2-[1H-benzotriazol-1-yl]acrylonitriles were able to act like tubulin binding agents, the effects on cell cycle distribution of the most active compounds (1, 2a, 3 and 4) were analyzed in K562 cells. A detailed molecular modeling study of the putative binding mode of this series of compounds on tubulin is also reported.     

Synthesis and anticancer activity of new 2-aryl-4h-3,1-benzothiazines

New compounds of 2-aryl-4H-3,1-benzothiazine set were synthesized and tested for their antiproliferative activity as part of our research in the antitumor field. The title compounds were obtained by the reaction of aryl-modified sulfinylbis((2,4-dihydroxyphenyl)methanethione) with 2-aminobenzyl alcohols. The reaction proceeded through thiobenzanilide intermediates, which were converted to the 4H-3,1-benzothiazine fused ring by an endocyclization process. The structures of compounds were identified from elemental, IR, (1) H-NMR, (13) C-NMR, and MS spectra analyses. The cytotoxicity in vitro against four human cancer cell lines was determined. The antiproliferative properties of some compounds were more beneficial than cisplatin studied comparatively.     

Apoptogenic activity and toxicity studies of a cytotoxic protein (BMP1) from the aqueous extract of common Indian toad (Bufo melanostictus Schneider) skin

A protein (BMP1) was purified from common Indian toad (Bufo melanostictus, Schneider) skin through DEAE cellulose ion exchange chromatography and high performance liquid chromatography. The molecular weight of the BMP1 was found to be 79 kDa. BMP1 (0.5 and 1 mg/kg/day, i.p.) significantly decreased the number of viable Ehrlich ascites carcinoma (EAC) cells, thereby increased the lifespan of EAC bearing mice (p < 0.001). MTT values reduced significantly with the treatment of BMP1 (0.5 and 1.0 mg/kg/day, i.p. for 3 days) on EAC cells indicated its antiproliferative activity. This was also supported by flow-cytometric data on the cell cycle arrest at G1 in EAC cells. BMP1 (1 mg/kg) reduced the solid tumor weight and volume of about three times further support the antiproliferative nature. Fluorescence and confocal microscopic study on EAC cells after BMP1 (0.5 mg/kg/day, i.p. for 3 days) treatment indicated certain features of apoptosis, like nuclear fragmentation, membrane blebbing, and vacuolization of cells. DNA fragmentation was clearly observed in alkaline comet assay. Apoptosis induced by BMP1 was further confirmed through flow-cytometric analysis of annexin-V binding study, sub-G1 arrest in the cell cycle and found to be mediated through caspase 3 dependent pathway. LD50 of BMP1 was found to be 12.2 mg/kg, i.p. in male Swiss albino mice. BMP1 treatment at 0.5 mg/kg and 1.0 mg/kg for 10 days did not alter any hematological and biochemical parameters in mice, but after 30 days of treatment produce significant rise in total leucocyte count, neutrophil percentage, serum urea, creatinine, GOT, LDH and decrease in lymphocyte percentage as compared to respective control. In conclusion, BMP1, a protein molecule isolated from Indian toad (B. melanostictus, Schneider) skin, showed antiproliferative and apoptogenic activity on EAC cancer cell with limited toxicity.     

Anticancer Effects of Curcuma C20-Dialdehyde against Colon and Cervical Cancer Cell Lines

Background: Recent attention on chemotherapeutic intervention against cancer has been focused ondiscovering and developing phytochemicals as anticancer agents with improved efficacy, low drug resistanceand toxicity, low cost and limited adverse side effects. In this study, we investigated the effects of CurcumaC20-dialdehyde on growth, apoptosis and cell cycle arrest in colon and cervical cancer cell lines. Materials andMethods: Antiproliferative, apoptosis induction, and cell cycle arrest activities of Curcuma C20-dialdehydewere determined by WST cell proliferation assay, flow cytometric Alexa fluor 488-annexin V/propidium iodide(PI) staining and PI staining, respectively. Results: Curcuma C20 dialdehyde suppressed the proliferation ofHCT116, HT29 and HeLa cells, with IC50 values of 65.4±1.74 μg/ml, 58.4±5.20 μg/ml and 72.0±0.03 μg/ml,respectively, with 72 h exposure. Flow cytometric analysis revealed that percentages of early apoptotic cellsincreased in a dose-dependent manner upon exposure to Curcuma C20-dialdehyde. Furthermore, exposure tolower concentrations of this compound significantly induced cell cycle arrest at G1 phase for both HCT116 andHT29 cells, while higher concentrations increased sub-G1 populations. However, the concentrations used in thisstudy could not induce cell cycle arrest but rather induced apoptotic cell death in HeLa cells. Conclusions: Ourfindings suggest that the phytochemical Curcuma C20-dialdehyde may be a potential antineoplastic agent forcolon and cervical cancer chemotherapy and/or chemoprevention. Further studies are needed to characterizethe drug target or mode of action of the Curcuma C20-dialdehyde as an anticancer agent.