Biological Evaluation of an Antibiotic DC-81–Indole Conjugate Agent in Human Melanoma Cell Lines

Pyrrolo[2, 1-c][1, 4]benzodiazepines (PBDs) are potent inhibitors of nucleic acid synthesis because of their ability to recognize and bind to specific sequences of DNA and form a labile covalent adduct. DC-81, an antitumor antibiotic produced by Streptomyces species, is a PBD. We combined DC-81 and an indole carboxylate moiety to synthesize a hybrid designed to have much higher sequence selectivity in DNA interactivity. In this paper, the cytotoxic potency of the hybrid in human melanoma cell lines was studied. XTT assay demonstrated that the DC-81-indole conjugate possessed cytotoxicity against human melanoma cell lines

In Vitro

Infection with Helicobacter pylori is strongly associated with gastric cancer and gastric adenocarcinoma. WHO classified H. pylori as a group 1 carcinogen in 1994. Impatiens balsamina L. has been used as indigenous medicine in Asia for the treatment of rheumatism, fractures and fingernail inflammation. In this study, we isolated anti-H. pylori compounds from this plant and investigated their anti- and bactericidal activity. Compounds of 2-methoxy-1,4-naphthoquinone (MeONQ) and stigmasta-7,22-diene-3β-ol (spinasterol) were isolated from the pods and roots/stems/leaves of I. balsamina L., respectively. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) for MeONQ were in the ranges of 0.156–0.625 and 0.313–0.625 μg mL−1, respectively, and in the ranges of 20–80 μg mL−1 both of MICs and MBCs for spinasterol against antibiotic (clarithromycin, metronidazole and levofloxacin) resistant H. pylori. Notably, the activity of MeONQ was equivalent to that of amoxicillin (AMX). The bactericidal H. pylori action of MeONQ was dose-dependent. Furthermore, the activity of MeONQ was not influenced by the environmental pH values (4–8) and demonstrated good thermal (121°C for 15 min) stability. MeONQ abounds in the I. balsamina L. pod at the level of 4.39% (w/w db). In conclusion, MeONQ exhibits strong potential to be developed as a candidate agent for the eradication of H. pylori infection

Biological Evaluation of an Antibiotic DC-81–Indole Conjugate Agent in Human Melanoma Cell Lines

Pyrrolo[2, 1-c][1, 4]benzodiazepines (PBDs) are potent inhibitors of nucleic acid synthesis because of their ability to recognize and bind to specific sequences of DNA and form a labile covalent adduct. DC-81, an antitumor antibiotic produced by Streptomyces species, is a PBD. We combined DC-81 and an indole carboxylate moiety to synthesize a hybrid designed to have much higher sequence selectivity in DNA interactivity. In this paper, the cytotoxic potency of the hybrid in human melanoma cell lines was studied. XTT assay demonstrated that the DC-81-indole conjugate possessed cytotoxicity against human melanoma cell lines

ZnBr₂‑Mediated Cascade Reaction of <i>o</i>‑Alkoxy Alkynols: Synthesis of Indeno[1,2‑<i>c</i>]chromenes

A Lewis acid-mediated cascade annulation of <i>o</i>-alkoxy alkynols in the presence of ZnBr₂ has been developed. The cascade cyclization proceeds through a 5-<i>exo</i>-dig cyclization followed by a Friedel–Crafts reaction and ring-opening sequence to synthesize indeno­[1,2-<i>c</i>]­chromenes. This protocol provides a broad substrate scope in moderate to good yields with high regioselectivity. The reaction with benzo-fused cycloalkyl ketones gave an unexpected alkyne C–C bond cleavage resulting in fused polycycles

Palladium-Catalyzed Intramolecular Cross-Dehydrogenative Coupling: Synthesis of Fused Imidazo[1,2a]pyrimidines and Pyrazolo[1,5a]pyrimidines

A palladium-catalyzed intramolecular dehydrogenative coupling reaction was developed for the synthesis of fused imidazo[1,2-a]pyrimidines and pyrazolo[1,5-a]- pyrimidines. The developed protocol provides a practical approach for the synthesis of biologically important substituted pyrimidines from easily available substrates, with a broad substrate scope under mild reaction conditions

Palladium-Catalyzed Double-Isocyanide Insertion via Oxidative N–O Cleavage of Acetyl Oximes: Syntheses of 2<i>H</i>‑Pyrrol-2-imines

The palladium-catalyzed reaction of acetyl oximes with isocyanides was developed for the synthesis of 2<i>H</i>-pyrrol-2-imines. The key steps were (i) generation of an enamido-palladium­(II) species, (ii) migratory double-isocyanide insertion, and (iii) cyclization. The scope of the synthesis of some 2<i>H</i>-pyrrol-2-imines was extended to the synthesis 1<i>H</i>-pyrrole-2,3-dione/1<i>H</i>-benzo­[<i>g</i>]­indole-2,3-dione derivatives via acid hydrolysis in a sequential one-pot manner

BF₃‑Etherate-Promoted Cascade Reaction of 2‑Alkynylanilines with Nitriles: One-Pot Assembly of 4‑Amido-Cinnolines

A BF₃-etherate-promoted cascade reaction of nitriles with 2-alkynylanilines is described. This method achieves the formation of two new C–N bonds through a reaction sequence of diazotization with <i>t</i>-BuONO, nucleophilic addition of the alkyne to the BF₃-coordinated diazonium ion, followed by nitrile addition to the intermediary vinyl cation and hydrolysis. The method provides efficient and general access to a variety of 4-amido-cinnolines. Notable features of the method include its broad functional group tolerance and avoidance of transition metals