Xue-Quan Wang

Design, synthesis and biological evaluation of novel hybrid compounds of imidazole scaffold-based 2-benzylbenzofuran as potent anticancer agents.

A series of novel hybrid compounds between 2-benzylbenzofuran and imidazole has been prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the existence of benzimidazole ring and substitution of the imidazolyl-3-position with a naphthylacyl or 4-methoxyphenacyl group were vital for modulating cytotoxic activity. In particular, hybrid compounds 46 and 47 were found to be the most potent derivatives against 5 strains human tumor cell lines and more active than cisplatin (DDP), and exhibited cytotoxic activities selectively against breast carcinoma (MCF-7) and myeloid liver carcinoma (SMMC-7721), respectively.

Silica Gel-Mediated Amide Bond Formation: An Environmentally Benign Method for Liquid-Phase Synthesis and Cytotoxic Activities of Amides

An efficient, functional group tolerable, and environmentally benign process for the synthesis of amides was developed. No activation reagents or scavengers are required in this process. Purification of desired compounds is easy, rapid, and cost-effective. This protocol provides an alternative for the combinatorial liquid-phase synthesis of amide libraries for drug discovery. By this method, a number of amides were prepared and evaluated in vitro against a panel of human tumor cell lines. Cinnamic amide IV-4 was found to be the most potent compound synthesized against four human tumor cell lines.

Synthesis and antitumor activities of novel dibenzo[b,d]furan-imidazole hybrid compounds.

A series of novel hybrid compounds between dibenzo[b,d]furan and imidazole has been prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the existence of benzimidazole ring, and the substitution of the imidazolyl-3-position with a naphthylacyl or 4-methoxyphenacyl group, were vital for modulating cytotoxic activity. In particular, hybrid compound 60 was found to be the most potent derivatives against all of human tumor cell lines investigated, while compound 49 was found to be more selective against breast carcinoma (MCF-7) and myeloid liver carcinoma (SMMC-7721). Compound 60 can induce the G1 phase cell cycle arrest and apoptosis in SMMC-7721 cells.

Enantioselective total synthesis of (+)-brazilin, (−)-brazilein and (+)-brazilide A

An enantioselective strategy for the synthesis of (+)-brazilin, (-)-brazilein and (+)-brazilide A has been developed. A Lewis acid mediated lactonization established the novel fused bis-lactone core of brazilide A and finalized the first total synthesis of (+)-brazilide A.

Synthesis and cytotoxic activities of novel hybrid 2-phenyl-3-alkylbenzofuran and imidazole/triazole compounds

A series of novel hybrid compounds of 2-phenyl-3-alkylbenzofuran and imidazole or triazole were prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the 2-ethyl-imidazole ring, and substitution of the imidazolyl-3-position with a 2-bromobenzyl or naphthylacyl group, were vital for modulating inhibitory activity. In particular, hybrid compound 31 was found to be the most potent derivative with IC₅₀ values of 0.08-0.55 μM against five strains human tumor cell lines and was found to be more selective against breast carcinoma (MCF-7) and colon carcinoma (SW480) (IC₅₀ values 40.8-fold and 40.1-fold lower than cisplatin (DDP)).

Design, synthesis and cytotoxic activities of novel hybrid compounds between dihydrobenzofuran and imidazole

A series of novel hybrid compounds between dihydrobenzofuran and imidazole has been prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that substitution of the imidazolyl-1-position with an electron-donating dihydrobenzofuran, and the imidazolyl-3-position with a naphthylacyl or electron-rich phenacyl group, were vital for modulating cytotoxic activity.

Synthesis and antitumor activity of novel N-substituted carbazole imidazolium salt derivatives

A series of novel N-substituted carbazole imidazolium salt derivatives has been prepared and investigated for their cytotoxic activity against five human tumor cell lines by MTS assay. The results indicated that the existence of 5,6-dimethyl-benzimidazole ring, substitution of the imidazolyl-3-position with a 2-bromobenzyl or naphthylacyl group, as well as alkyl chain length between carbazole and imidazole ring were important for the antitumor activity. Compound 61, bearing a 2-bromobenzyl substituent at position-3 of the 5,6-dimethyl-benzimidazole, showed powerful inhibitory activities and was more selective to HL-60, SMMC-7721, MCF-7 and SW480 cell lines with IC50 values 0.51–2.48 μM. Mechanism of action studies revealed that this new compound could remarkably induce cell cycle arrest and apoptosis in SMMC-7721 cells. This work provides alternative novel way for future drug development based on carbazole and imidazolium salt scaffolds.

Novel Tricyclic Indeno[5,6-b]furan-imidazole Hybrid Compounds: Design, Synthesis and Antitumor Activity

A series of novel hybrid compounds between tricyclic indeno[5,6-b] furan and imidazole has been prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the existence of benzimidazole ring and substitution of the imidazolyl-3-position with a naphthylacyl group were vital for modulating cytotoxic activity. In particular, hybrid compound 26 was found to be the most potent compound against 5 strains human tumor cell lines and more active than cisplatin (DDP), while compound 18 was more selective towards breast carcinoma (MCF-7) and colon carcinoma (SW480) with IC50 value 3.4-fold and 4.3-fold more sensitive to DDP.