TY - JOUR
T1 - Leucettamine B analogs and their carborane derivative as potential anti-cancer agents
T2 - Design, synthesis, and biological evaluation
AU - Hsu, Ming Hua
AU - Hsieh, Cheng Ying
AU - Kapoor, Mohit
AU - Chang, Jui Hsun
AU - Chu, Hsueh Liang
AU - Cheng, Tsai Mu
AU - Hsu, Kai Cheng
AU - Lin, Tony Eight
AU - Tsai, Fu Yuan
AU - Horng, Jia Cherng
N1 - Funding Information:
We thank National Changhua University of Education , National Tsing Hua University , and Ministry of Science and Technology of the Republic of China for financial support. Authors thank to Ms. Miranda Jane Loney (ABRC, Academia Sinica, Taiwan) for her attentive editing of this manuscript. This work was supported by the Ministry of Science and Technology ( MOST 106-2113-M-018-008 ) ( MOST 107-2113-M-018-008 ) ( MOST 108-2113-M-018-009 ).
PY - 2020/5
Y1 - 2020/5
N2 - Leucettamine B is a natural product found in marine sponge Leucetta microraphis. Several of analogs of its family, such as aplysinopsine and clathridine, are medicinally active molecules which have applications in many pharmaceuticals and healthcare products; however, thus far, leucettamine B has not been studied. In this report, we describe the synthesis of a new class of analogs of leucettamine B obtained by Knoevenagel condensation using a microwave reactor. The 25 newly synthesized compounds were tested against MDA-MB-468, SW480, and Mahlavu cell lines for anticancer activity. Among them, the carborane-based compound (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-3-(1-closo-carboranyl)-2-thioxo -thiazolidin-4-one (49) and (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-3-(2-(pyrrolidin-1-yl)ethyl)-2-thioxothiazolidin-4-one (31) derivatives were found to have the most potential for use against tumor cells. The carborane derivative 49 had the lowest IC50 value against the SW480 cell line (4.7 μM) and the Mahlavu (6.6 μM) cell line. Furthermore, compound 31 also had a low IC50 value against SW480 (7.5 μM). Our research shows that leucettamine B analogs might have potential for use in cancer chemotherapy.
AB - Leucettamine B is a natural product found in marine sponge Leucetta microraphis. Several of analogs of its family, such as aplysinopsine and clathridine, are medicinally active molecules which have applications in many pharmaceuticals and healthcare products; however, thus far, leucettamine B has not been studied. In this report, we describe the synthesis of a new class of analogs of leucettamine B obtained by Knoevenagel condensation using a microwave reactor. The 25 newly synthesized compounds were tested against MDA-MB-468, SW480, and Mahlavu cell lines for anticancer activity. Among them, the carborane-based compound (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-3-(1-closo-carboranyl)-2-thioxo -thiazolidin-4-one (49) and (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-3-(2-(pyrrolidin-1-yl)ethyl)-2-thioxothiazolidin-4-one (31) derivatives were found to have the most potential for use against tumor cells. The carborane derivative 49 had the lowest IC50 value against the SW480 cell line (4.7 μM) and the Mahlavu (6.6 μM) cell line. Furthermore, compound 31 also had a low IC50 value against SW480 (7.5 μM). Our research shows that leucettamine B analogs might have potential for use in cancer chemotherapy.
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U2 - 10.1016/j.bioorg.2020.103729
DO - 10.1016/j.bioorg.2020.103729
M3 - Article
AN - SCOPUS:85081269469
VL - 98
JO - Bioorganic Chemistry
JF - Bioorganic Chemistry
SN - 0045-2068
M1 - 103729
ER -