Differential Effect of 4H-Benzo[d] [1, 3]oxazines on the Proliferation of Breast Cancer Cell Lines.

BACKGROUND: A family of 4H-benzo[d][1,3]oxazines were obtained from a group of N-(2-alkynyl)aryl benzamides precursors via gold(I) catalysed chemoselective 6-exo-dig C-O cyclization. METHOD: The precursors and oxazines obtained were studied in breast cancer cell lines MCF-7, CAMA-1, HCC1954 and SKBR-3 with differential biological activity showing various degrees of inhibition with a notable effect for those that had an aryl substituted at C-2 of the molecules. 4H-benzo[d][1,3]oxazines showed an IC50 rating from 0.30 to 157.4 µM in MCF-7, 0.16 to 139 in CAMA-1, 0.09 to 93.08 in SKBR-3, and 0.51 to 157.2 in HCC1954 cells. RESULTS: We observed that etoposide is similar to benzoxazines while taxol effect is more potent. Four cell lines responded to benzoxazines while SKBR-3 cell line responded to precursors and benzoxazines. Compounds 16, 24, 25 and 26 have the potent effect in cell proliferation inhibition in the 4 cell lines tested and correlated with oxidant activity suggesting a possible mechanism by ROS generation. CONCLUSION: These compounds represent possible drug candidates for the treatment of breast cancer. However, further trials are needed to elucidate its full effect on cellular and molecular features of cancer.

Ningalins, Pyrrole-Bearing Metabolites Isolated from Didemnum spp. Synthesis and MDR-Reversion Activity in Cancer Therapy.

Multi-Drug Resistance (MDR) is one of the most frequent problems observed in the course of cancer chemotherapy. Cells under treatment, tend to develop survival mechanisms to drug-action thus generating drug-resistance. One of the most important mechanism to get it is the over expression of P-gp glycoprotein, which acts as an efflux-pump releasing the drug outside of the cancer cell. A strategy for a succesfull treatment consists in the co-administration of one compound that acts against P-gp and another which acts against the cell during chemotherapy. Ningalins are pyrrole-containing naturally occurring compounds isolated mainly from the marine tunicate Didemnum spp and also they are some of the top reversing agents in MDR treatment acting on P-gp. Considering the relevance displayed for some of these isolated alkaloids or their core as a drug for co-administration in cancer therapy, all the total synthesis described to date for the members of ningalins family are reviewed herein.

Iodine(III) reagents for oxidative aromatic halogenation.

Iodine(III) reagents have attracted chemical relvance in organic synthesis by their use as safe, non-toxic, green and easy to handle reagents in different transformations. These characteristics make them important alternatives to procedures involving hazardous and harsh reaction conditions. Their versatility as oxidants has been exploited in the functionalization of different aromatic cores, which allow the introduction of several groups. Metal-free arylation using iodine(III) reagents is by far one of the most described topics in the literature; however, other highly relevant non-aromatic groups have been also introduced. Herein, we summarize the most representative developed procedures for the functionalization of aryls and heteroaryls by introducing halogens, using different iodine(III) reagents.

Gold(I)-Catalyzed Synthesis of 4H-Benzo[d][1,3]oxazines and Biological Evaluation of Activity in Breast Cancer Cells.

The first gold(I)-catalyzed cycloisomerization procedure applied to the synthesis of substituted 4H-benzo[d][1,3]oxazines has been developed starting from N-(2-alkynyl)aryl benzamides. The chemoselective oxygen cyclization via the 6-exo-dig pathway yielded the observed heterocycles in modest to good chemical yields under very mild reaction conditions. The obtained oxazines were assayed on the breast cancer (BC)-derived cell lines MCF-7 and HCC1954 with differential biological activity. The newly synthesized 4H-benzo[d][1,3]oxazine compounds showed several degrees of cell proliferation inhibition with a remarkable effect for those compounds having a substituted aryl at C-2 of the molecules. The 4H-benzo[d][1,3]oxazines showed an IC50 ranking from 3.1 to 95 µM in MCF-7 and HCC1954 cells. These compounds represent potential drug candidates for BC treatment. However, additional assays are needed to elucidate their complete effect over the cellular and molecular hallmarks of cancer.

Novel 2-aryl-4-aryloxyquinoline-based fungistatics for Mucor circinelloides. Biological evaluation of activity, QSAR and docking study.

Zygomycetes are ubiquitous saprophytes in natural environments which transform organic matter. Some zygomycetes of gender Mucor have attracted interest in health sector. Due to its ability as opportunistic microorganisms infecting immuno-compromised people and to the few available pharmacological treatments, the mucormycosis is receiving worldwide attention. Concerning to the pharmacological treatments, some triazole-based compounds such as fluconazole are extensively used. Nevertheless, we focused in the quinolines since they are broadly used models for the design and development of new synthetic antifungal agents. In this study, the fungistatic activity on M. circinelloides of various 2-aryl-4-aryloxyquinoline-based compounds was discovered, and in some cases, it resulted better than reference compound fluconazole. These quinoline derivatives were synthesized via the Csp2-O bond formation using diaryliodonium(III) salts chemistry. A QSAR study was carried out to quantitatively correlate the chemical structure of the tested compounds with their biological activity. Also, a docking study to identify a plausible action target of our more active quinolines was carried out. The results highlighted an increased activity with the fluorine- and nitro-containing derivatives. In light of the few mucormycosis pharmacological treatments, herein we present some non-described molecules with excellent in vitro activities and potential use in the mucormycosis treatment.

Iodine(III)-Mediated, Controlled Di- or Monoiodination of Phenols.

An oxidative procedure for the electrophilic iodination of phenols was developed by using iodosylbenzene as a nontoxic iodine(III)-based oxidant and ammonium iodide as a cheap iodine atom source. A totally controlled monoiodination was achieved by buffering the reaction medium with K3PO4. This protocol proceeds with short reaction times, at mild temperatures, in an open flask, and generally with high yields. Gram-scale reactions, as well as the scope of this protocol, were explored with electron-rich and electron-poor phenols as well as heterocycles. Quantum chemistry calculations revealed PhII(OH)·NH3 to be the most plausible iodinating active species as a reactive "I+" synthon. In light of the relevance of the iodoarene moiety, we present herein a practical, efficient, and simple procedure with a broad functional group scope that allows access to the iodoarene core unit.