Multicomponent synthesis of some new (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-dithiocarbamates and their in vitro anti-proliferative activity against CaSki, MDA-MB-231 and SK-Lu-1 tumour cells as apoptosis inducing agents without necrosis

Abstract

Identification of a new class of antitumor agent capable to induce apoptosis without triggering necrotic cell death event is challenging. The present communication describes the multicomponent synthesis of seven new (1S,4S)-2,5-diazabicyclo[2.2.1]heptane-dithiocarbamates and their in vitro antiproliferative activity on cervical cancer cell line (CaSki), breast cancer cell line (MDA-MB231), lung cancer cell line (SK-Lu-1) and human lymphocytes. Among the synthesized dithiocarbamates, compound 9e displayed significant antiproliferative activity without inducing any necrotic cell death (both on tumour cells and lymphocytes) and induced apoptosis in tumor cells by the caspase dependent apoptotic pathway. The compound 9e also exhibited greater tumor selectivity than human lymphocytes. In silico ADME predictions revealed that compound 9e has the potential to be developed as a drug candidate. Rapid chemical modifications of this lead are thus highly necessary for further investigation as a drug like safer antitumor candidate and also to achieve compounds with better activity profile.

Juggling Surface Charges of 2D Niobium Carbide MXenes for a Reactive Oxygen Species Scavenging and Effective Targeting of the Malignant Melanoma Cell Cycle into Programmed Cell Death

“…In contrast, the contribution of apoptotic cells after the exposition of melanoma cultures (Figure 4c,d) to both nanostructures is concentration related and amounts from about 5% (in the case of pristine materials) to even over 20% (for nanoflakes coated by PLL), which is desirable; the induction of apoptosis is considered as one of most successful strategies in cancer treatment. 26,27 A number of works have explored the mechanisms involved in the toxicity of 2D materials such as graphene and indicated the critical role of programmed cell death. 28−30 Until now, there was lack of substantial information on MXenes as an apoptosis agent.…”

“…The population of HaCaT cells that underwent apoptosis is negligiblethe obtained data suggest necrosis/late apoptosis as the most possible mechanism of action for Nb-based MXenes toward normal keratinocytes (Figure a,b). In contrast, the contribution of apoptotic cells after the exposition of melanoma cultures (Figure c,d) to both nanostructures is concentration related and amounts from about 5% (in the case of pristine materials) to even over 20% (for nanoflakes coated by PLL), which is desirable; the induction of apoptosis is considered as one of most successful strategies in cancer treatment. , A number of works have explored the mechanisms involved in the toxicity of 2D materials such as graphene and indicated the critical role of programmed cell death. − Until now, there was lack of substantial information on MXenes as an apoptosis agent . As can be seen, switching the surface charge of tested MXenes results in obtaining important biological effect in vitro such as triggering apoptosis, i.e., programmed cell death.…”

Crystal structure of (1S,4S)-2,5-diazoniabicyclo[2.2.1]heptane dibromide

“…Derivatives of the bicyclic nucleus of 2,5-diazabicyclo[2.2.1]heptane comprise a wide family of biochemically active compounds (Murineddu et al, 2012), including antibiotics (McGuirk et al, 1992;Remuzon et al, 1993), vasodilating (Ló pez-Ortiz et al, 2014) and antitumor agents (Hamblett et al, 2007;Shchekotikhin et al, 2014;Gerstenberger et al, 2016;Laskar et al, 2017). A broad range of these compounds have been found to exhibit potency as nicotinic acetylcholine receptor ligands (Toma et al, 2002;Artali et al, 2005;Bunnelle et al, 2007;Anderson et al, 2008;Li et al, 2010;Beinat et al, 2015;Bertrand et al, 2015).…”