Synthesis and Antitumor Activity of Novel Heterocyclic Systems with Monoterpenic Skeleton Combining Dichlorocyclopropane and 1, 3, 4‐Thiadiazole Nucleus. Issue 21 (4th June 2020)

• Record Type: Journal Article
• Authors: Oubella, Ali; Fawzi, Mourad; Auhmani, Aziz; Riahi, Abdelkhalek; Morjani, Hamid; Robert, Anthony; Ait Itto, Moulay Y.
• Is Part Of: ChemistrySelect. Volume 5:Issue 21(2020)
• Page Start: 6403
• Page End: 6406
• Publication Date: 2020-06-04
• Subjects: (R)-Carvone -- Cytotoxic Activity -- Nitrilimines -- 1, 3-Dipolar cycloaddition -- 1, 3, 4-thiadiazoles; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202001284
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: A series of C(2)‐N(4)‐disubstituted 1, 3, 4‐thiadiazoles bearing dichlorocyclopropane, have been prepared from (R)‐carvone 1 in a three‐step procedure. First, (R)‐carvone was treated with dichlorocarbene, generated in‐situ from chloroform using PTC technique. The resulting dichlorocyclopropane 2 was then converted into thiosemicarbazone derivatives 3 a –c before being transformed peri‐selectively and efficiently (up to 80 % yield) into their corresponding 1, 3, 4‐thiadiazoles (6 a –d and 7 a –c ) via 1, 3‐dipolar cycloaddition reaction with diarylnitrilimines 4 a –d and N‐aryl‐C‐ethoxycarbonyl‐nitrilimines 5 a –c . The structures of all the newly synthesized cyclopropanic 1, 3, 4‐thiadiazoles 6 a –d and 7 a –c were fully identified on the basis of their HRMS and NMR (1D & 2D) spectral data. The evaluation of compounds 2, 3 a –c, 6 a –d and 7 a –c, against HT‐1080 fibrosarcoma, breast adenocarcinoma (MCF‐7 and MDA‐MB‐231), and lung carcinoma A‐549 cells, using viability testing (MTT) showed promising antitumor activity, especially for compounds 3 a, 6 b and 6 c for which the IC50 values, against HT‐1080 fibrosarcoma, were respectively 18.92, 16.12 and 15.37 (μM). Abstract : An efficient and chemoselective three‐step procedure was carried out from (R)‐carvone to access new C(2)‐N(4)‐disubstituted 1, 3, 4‐thiadiazoles paired with a dichlorocyclopropane core. These newly prepared dichlorocyclopropanic thiadiazoles have revealed interesting antitumor activity.