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1.
Bioorg Med Chem ; 29: 115870, 2021 01 01.
Article in English | MEDLINE | ID: mdl-33221062

ABSTRACT

As an oncometabolite, lactate plays a very important role in tumor proliferation, metastasis, angiogenesis, immune escape and other tumor biological functions. Pharmacological inhibition oflactate transport has been viewed as a promising therapeutic strategy to target a range of human cancers. In this study, a series of new coumarin-3-carboxylic acid derivatives 5a-t and 9a-b were synthesized and evaluated as lactate transport inhibitors. Their cytotoxic activity has been tested against three cell lines high-expressing and low-expressing monocarboxylate transporter 1 (MCT1) which acts as the main carrier for lactate. Compound 5c-e, 5g-i and 5m-o showed significant cytotoxicity and good selectivity against Hela and HCT116 cell lines with high MCT1 expression. Notably, coumarin-3-hydrazide 5o, the lead molecule with the most potent cytotoxic activity, exhibitedsignificant anti-proliferationandapoptosisinductioneffects. Further studies revealed that compound 5o decreased the expression level of target MCT1, and suppressed the energetic metabolism of Hela and HCT116 cells byremarkably reducing glucoseconsumptionandlactate production. Additionally, compound 5o induced intracellular lactate accumulation and inhibited lactate uptake, which implied that it blocked lactate transport via MCT1. These results indicate a good start point for the development of lactate transport inhibitors as new anticancer agents.


Subject(s)
Antineoplastic Agents/pharmacology , Coumarins/pharmacology , Lactates/antagonists & inhibitors , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Proliferation/drug effects , Coumarins/chemical synthesis , Coumarins/chemistry , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Lactates/metabolism , Molecular Structure , Structure-Activity Relationship , Tumor Cells, Cultured
2.
Chem Cent J ; 12(1): 136, 2018 Dec 19.
Article in English | MEDLINE | ID: mdl-30564982

ABSTRACT

A facile and efficient palladium-catalyzed borylation of aryl (pseudo)halides at room temperature has been developed. Arylboronic esters were expeditiously assembled in good yields and with a broad substrate scope and good functional group compatibility. This approach has been successfully applied to the one-pot two-step borylation/Suzuki-Miyaura cross-coupling reaction, providing a concise access to biaryl compounds from readily available aryl halides. Furthermore, a parallel synthesis of biaryl analogs is accomplished at room temperature using the strategy, which enhances the practical usefulness of this method.

3.
RSC Adv ; 8(25): 13643-13648, 2018 Apr 11.
Article in English | MEDLINE | ID: mdl-35539348

ABSTRACT

A highly efficient room-temperature borylation strategy of aryl chlorides is described. Utilizing Buchwald's second-generation preformed catalyst, boronate esters were obtained for a wide range of substrates in high yield. The method was also applied to Suzuki-Miyaura cross-coupling reaction in a one-pot two-step sequential manner, providing a facile and convenient access to the direct synthesis of biaryl compounds from aryl chlorides.

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