Synthesis, cytotoxic, anti-lipoxygenase and anti-acetylcholinesterase capacities of novel derivatives from harmine

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 31; no. sup1; pp. 23 - 33
• Main Authors: Filali, Insaf, Belkacem, Mohamed Amine, Ben Nejma, Aymen, Souchard, Jean Pierre, Ben Jannet, Hichem, Bouajila, Jalloul
• Format: Journal Article
• Language: English
• Published: ABINGDON Taylor & Francis 01.11.2016; Informa Healthcare
• Subjects: 5-lipoxygenase; Acetylcholinesterase; Acetylcholinesterase - metabolism; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biochemistry & Molecular Biology; Cell Line, Tumor; Cell Proliferation - drug effects; Chemical Sciences; Chemistry, Medicinal; Cholinesterase Inhibitors - chemical synthesis; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; cytotoxic; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Harmine - analogs & derivatives; Harmine - chemical synthesis; Harmine - chemistry; Humans; hydrazide; Life Sciences & Biomedicine; Lipoxygenase - metabolism; Lipoxygenase Inhibitors - chemical synthesis; Lipoxygenase Inhibitors - chemistry; Lipoxygenase Inhibitors - pharmacology; Molecular Structure; Pharmacology & Pharmacy; Science & Technology; Structure-Activity Relationship; triazoles; DESIGN; triazoles; ALZHEIMER; Acetylcholinesterase; L; hydrazide; IN-VITRO; HYDRAZONE DERIVATIVES; ANTICANCER; ANTIOXIDANT; BIOLOGICAL EVALUATION; 5-lipoxygenase; cytotoxic; ALKALOIDS
• ISSN: 1475-6366; 1475-6374
• DOI: 10.3109/14756366.2016.1163342

We synthesized two series of new hydrazide harmine derivatives. The reaction of harmine 1 with ethyl acetate chloride afforded the corresponding ethyl ester 2. The treatment of 2 with hydrazine hydrate gave the hydrazide 3 which further converted into hydrazones 4a-j and dihydrazides 5a-c. A series of new triazoles 7a-f has also been prepared from the suitable propargyl harmine 6. The synthesized derivatives were characterized by 1 H-NMR, 13 C-NMR, and HRMS and evaluated for their activities against MCF7, HCT116 OVCAR-3, acetylcholinesterase and 5-lipoxygenase. The most hydrazones derivatives 4a-j have a good cytotoxic activity against all cell lines, when 4a, 4d, 4f and 4 g are more active than 1 (against OVCAR-3 IC 50 16.7-2.5 μM). The compound 6 was the most active (IC 50  =   1.9 μM) against acetylcholinesterase. Some compounds exhibited significant activity against 5-lipoxygenase (IC 50  =   30.9-63.1 μM).