Synthesis and antitumor activity of tetrahydrocarbazole hybridized with dithioate derivatives

Abstract

The present study reported the synthesis of tetrahydrocarbazoles hybridized with dithioate derivatives. Three series were synthesized namely alkyl dithiocarbonates (4a-d), heterocyclic dithiocarbamates (6a-g) and dialkyl dithiocarbamate (7). The synthesized compounds were tested in vitro on human breast adenocarcinoma cell line (MCF7) and the human colon tumor cell line (HCT116). Most of the synthesized compounds exploited potent antitumor activity, especially compound 6f [4-chlorophenylpiperazine derivative], which showed cytotoxic activity against MCF7 superior to doxorubicin with IC 50 value of 7.24 nM/mL.

Exploring the diastereoselectivity for Fischer indolization of L-menthone under different conditions, spectral characterization, and biological activities of new (2R,4aS)-2,3,4,4a-tetrahydro-1H-carbazole analogs

“…13 C NMR (100 MHz, CDCl3, δ, ppm): 155.8 (C), 145.9 (C), 140.3 (C), 135.9/135.8 (d, C, J = 7.0 Hz), 113.2/112.9 (d, CH, J = 23.0 Hz), 111.8/111.6 (d, CH, J = 23.0 Hz), 110.9/110.8 (d, CH, J = 8.0 Hz), 65.0 (C), 40.7 (CH2), 33.7 (CH), 30.8 (CH2), 28.9 (CH), 24.9 (CH2), 22.2 (CH3), 17.8 (CH3), 17.5 (CH3). MS (EI, m/z (%)): 245 (M + , 68), 230 (73), 203 (60), 188 (14), 174 (7), 161 (100), 148 (9), 133 (10) (2,4-eq) = 4.2 Hz, 1H, 3-ax CH2), 1.40 (dm, J3-eq,3-ax = 15.0 Hz, 1H, 3-eq CH2), 1.27 (td, J4-ax,(3-ax,4-eq) = 14.1 Hz, J4-ax,3-eq = 3.8 Hz, 1H, 4-ax CH2), 1.22 (d, J12,11 = 6.9 Hz, 3H, 12-CH3), 0.84 (d, J10,2 = 7.2 Hz, 3H, 10-CH3), 0.27 (d, J13,11 = 6.7 Hz, 3H, 13-CH3). 13 (3-eq,4-ax) = 13.9 Hz, J3-ax,(2,4-eq) = 4.1 Hz, 1H, 3-ax CH2), 1.39 (dm, J3-eq,3-ax = 14.0 Hz, 1H, 3-eq CH2), 1.26 (td, J4-ax,(3-ax,4-eq) = 14.2 Hz, J4-ax,3-eq = 4.0 Hz, 1H, 4-ax CH2), 1.21 (d, J12,11 = 6.8 Hz, 3H, 12-CH3), 0.84 (d, J10,2 = 7.2 Hz, 3H, 10-CH3), 0.26 (d, J13,11 = 6.6 Hz, 3H, 13-CH3).…”

“…d, J8,7 = 7.4 Hz, 1H, H-8), 3.01 (q, J14,15 = 7.4 Hz, 2H, 14-CH2), 2.75 (dd, J1-eq,1-ax = 13.2 Hz, J1-eq,2 = 6.1 Hz, 1H, 1-eq CH2), 2.66 (d, J1-ax,2 = 13.0 Hz, 1H, 1-ax CH2), 2.50-2.48 (m, 1H, 2-CH), 2.36-2.29 (m, 2H, 4-eq CH2/11-CH), 2.01 (tt, J3ax,(3-eq,4-ax) = 13.9 Hz, J3-ax,(2-eq,4-eq) = 3.9 Hz, 1H, 3-ax CH2), 1.37 (dm, J3-eq,3-ax = 13.8 Hz, 1H, 3-eq CH2), 1.29 (t, J15,14 = 7.6 Hz, 3H, 15-CH3), 1.25-1.22 (m, 1H, 4-ax CH2), 1.20 (d, J12,11 = 6.9 Hz, 3H, 12-CH3), 0.82 (d, J10,2 = 7.2 Hz, 3H, 10-CH3), 0.24 (d, J13,11 = 6.7 Hz, 3H, 13-CH3). 13 (17), 171 (100), 156 (16), 143 (7), 128 (6), 115 (7), 91 (2). UV/Vis (CHCl3, λmax, nm, (ε)): 332 (0.55), 325 (0.56), 260 (1.50), 249 (1.61).…”

“…This class is widely distributed in nature and has gained immense attention of medicinal chemists as found as the main skeleton in many bioactive compounds [1]. These compounds showed biological properties such as P-type ATPase inhibitory activity as antifungal [2], DNA biosynthesis inhibitory activity as antibacterial [3], antiviral [4], neuroprotective [5], β-3-adrenoceptor agonist [6], antitumor [7], etc. (Figure 1).…”

Synthesis of Tris-Heterocycles via a Cascade IMCR/Aza Diels-Alder + CuAAC Strategy

“…Piperidine, morpholine, and diethylamine were incorporated as substituents of isocyanides 3a-c . These fragments can act as structural bioisosteres, preferably interacting with some amino acids allowing in some cases improve biological activity (Kalinsky and Weinstein, 1954; Sander et al, 2008; Meng et al, 2011; El-Nassan, 2015; Yu et al, 2015; Sato et al, 2017).…”

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

“…Literature revealed that many dithiocarbamate derivatives displayed potent anticancer activity ( Figure 1 ) both in in vitro and in vivo model and might act by induction of apoptosis 6 . Molecular hybridization technique had been widely adopted in designing new dithiocarbamate cytotoxic agents which includes tetrahydrocarbazole 7 , 1,2,3-triazoles 8 , quinazolines 9 , emetine 10 , chromones 11 , benzodioxole 12 dithiocarbamate derivatives, etc 13 , 14 . However, the molecular hybridization of dithiocarbamate with bridged bicyclic compounds to achieve new class of antiproliferative agents have not been reported so far.…”