Novel R-(+)-limonene-based thiosemicarbazones and their antitumor activity against human tumor cell lines

• Published in: European journal of medicinal chemistry Vol. 79; pp. 110 - 116
• Main Authors: Vandresen, Fábio, Falzirolli, Hugo, Almeida Batista, Sabrina A., da Silva-Giardini, Ana Paula B., de Oliveira, Diogo N., Catharino, Rodrigo R., Ruiz, Ana Lúcia T.G., de Carvalho, João E., Foglio, Mary Ann, da Silva, Cleuza Conceição
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 22.05.2014; Elsevier
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antitumor; Cell Line, Tumor; Cell Proliferation - drug effects; Chemistry, Medicinal; Cyclohexenes - chemistry; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; K562 Cells; Life Sciences & Biomedicine; MCF-7 Cells; Molecular Structure; Pharmacology & Pharmacy; Prostate cancer cells; R-(+)-limonene; Science & Technology; Stereoisomerism; Structure-Activity Relationship; Terpenes - chemistry; Thiosemicarbazide; Thiosemicarbazones; Thiosemicarbazones - chemical synthesis; Thiosemicarbazones - chemistry; Thiosemicarbazones - pharmacology; Prostate cancer cells; Thiosemicarbazide; R-(+)-limonene; Thiosemicarbazones; Antitumor; D-LIMONENE; CARVONE; PHASE-I; DERIVATIVES
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.03.086

In an attempt to develop potent and selective antitumor agents, a series of novel thiosemicarbazones derived from a natural monoterpene R-(+)-limonene was synthesized and their antitumor activity was evaluated. Overall, the majority of tested compounds exhibited considerable inhibitory effects on the growth of a wide range of cancer cell lines. Almost all of tested thiosemicarbazones were especially sensitive to prostate cells (PC-3). Derivatives 5, 6, 8, 9, 10, 11 and 13 presented the most potent antitumor activity against PC-3 cells. These compounds showed lower value of GI50 (0.04–0.05 μM) than the reference drug paclitaxel, besides a high selectivity for the same cell line. The 4-fluorobenzaldehyde derivative 10 was the most selective compound for prostate cells, while 2-hydroxybenzaldehyde derivative 8 was the most active compound, with potent antitumor activity against all tested cell lines. [Display omitted] •Synthesis of 19 new thiosemicarbazones containing the natural monoterpene R-(+)-limonene linked to N-4 position.•Antitumoral activity screening against ten human cancer cell lines.•The majority of synthesized compounds were sensitive to prostate cells PC-3.•Derivative p-fluorothiosemicarbazone 10 was the most selective compound against PC-3 cell.•Derivative o-hydroxythiosemicarbazone 8 was the most active compound against all tested tumor cell lines.