Synthesis and Anti-tumor Activity Evaluation of a Novel Series of Dithiocarbamates Bearing 1,2,3-Triazole and [1-Bi(4-fluorophenyl)methyl]piperazine Unit

1,2,3-Triazole-Containing Compounds as Anti–Lung Cancer Agents: Current Developments, Mechanisms of Action, and Structure–Activity Relationship

“…Additionally, the activity of 1,2,3-triazole-containing dibenzo [b, e][1,4]diazepin-11-one hybrid 83 (IC 50 : 0.71 μm, MTT assay) against A549 cells is much higher than that of 5fluorouracil (IC 50 : 3.47 μm), and this hybrid could induce the G2/M phase of cell cycle arrest and apoptosis, indicating that hybrid 83 could be used for further studies as anti-lung cancer candidates (Praveen Kumar et al, 2016). Some other compounds which are combined by 1,2,3-triazole and benzodiazepine/benzoxepine/dithiocarbamate/ deoxysalinomycin/myrrhanone B /phenanthrene/pyrano(2,3-c) phenazine/paeonol/naphthalimide/sesquiterpene/sulfonate ester/sapinofuranone/triterpene/thiourea/benzothiazinone/ benzoxazinone/furan/nimesulide (Kuntala et al, 2015;Poornima et al, 2015;Sudhapriya et al, 2015;Chandrashekhar et al, 2016;Reddy et al, 2016;Shaikh et al, 2016;Abdallah et al, 2017;Battula et al, 2017;Kumar et al, 2017;Lu et al, 2017;Mareddy et al, 2017;Mo et al, 2017;Nguyen et al, 2017;Narsimha et al, 2018;Ou et al, 2019;Yang et al, 2019;Jiang et al, 2020;Kanabar et al, 2020;Madasu et al, 2020;Qi et al, 2020;) also possess certain activity against lung cancer cell lines, but their activities are generally far inferior to those of the references. Hence, these derivatives still need further structural modifications.…”

Therapeutic potential of 1,2,3‐triazole hybrids for leukemia treatment

“…Besides the above-mentioned hybrids, 1,2,3-triazoleartemisinins, [97,98] 1,2,3-triazole-aziridines, [99,100] 1,2,3-triazoledithiocarbamates, [101] 1,2,3-triazole-indoles, [102] 1,2,3-triazolemollugin, [103] 1,2,3-triazole-D-(+)-pinitols, [104] 1,2,3-triazole-nerols, [105] 1,2,3-triazole-retinoids, [106] 1,2,3-triazole-salinomycin, [107] 1,2,3-triazoleethacrynic acids, [108] 1,2,3-triazole-curcumins, [109] benzotriazolehydrazones, [110] and 1,2,3-triazole-10,11-dihydro-9H-9,10- [3,4] epipyrroloanthracene-12,14(13H,15H)-diones [111] also possessed certain antileukemic activity. Amongst them, the 1,2,3-triazole-salinomycin hybrid 47 (Figure 8; IC 50 : 250 nM, MTT assay) was 2.3-and 136.8-fold more potent than salinomycin (IC 50 : 580 nM) and cisplatin (IC 50 :…”

“…Besides the above‐mentioned hybrids, 1,2,3‐triazole‐artemisinins, [ 97,98 ] 1,2,3‐triazole‐aziridines, [ 99,100 ] 1,2,3‐triazole‐dithiocarbamates, [ 101 ] 1,2,3‐triazole‐indoles, [ 102 ] 1,2,3‐triazole‐mollugin, [ 103 ] 1,2,3‐triazole‐ d ‐(+)‐pinitols, [ 104 ] 1,2,3‐triazole‐nerols, [ 105 ] 1,2,3‐triazole‐retinoids, [ 106 ] 1,2,3‐triazole‐salinomycin, [ 107 ] 1,2,3‐triazole‐ethacrynic acids, [ 108 ] 1,2,3‐triazole‐curcumins, [ 109 ] benzotriazole‐hydrazones, [ 110 ] and 1,2,3‐triazole‐10,11‐dihydro‐9 H ‐9,10‐[3,4]epipyrroloanthracene‐12,14(13 H ,15 H )‐diones [ 111 ] also possessed certain antileukemic activity. Amongst them, the 1,2,3‐triazole‐salinomycin hybrid 47 (Figure 8; IC 50 : 250 nM, MTT assay) was 2.3‐ and 136.8‐fold more potent than salinomycin (IC 50 : 580 nM) and cisplatin (IC 50 : 3.42 μM) against HL‐60 leukemia cells, but the SAR revealed that 1,2,3‐triazole moiety was not essential for the high activity [ 107 ] ; the 1,2,3‐triazole‐ethacrynic acid hybrids 48a,b (IC 50 : 310 and 290 nM, MTT assay) not only were highly active against HL‐60 leukemia cells, but also were comparable to doxorubicin (IC 50 : 50.1–700 nM and 20.2–650 vs. 2.1–120 nM) against A549, MCF‐7, PC3, U87‐MG, SKOV3, and HCT‐116 cancer cell lines [ 108 ] ; the 1,2,3‐triazole‐curcumin hybrids 49a,b (IC 50 : 3.13 and 3.95 μM, MTT assay) were around three times more active than curcumin (IC 50 : 10.51 μM) against CCRF‐CEM leukemia cells, and hybrid 49a decreased mitochondrial transmembrane potential, arrested SubG0 phase and induced apoptosis [ 109 ] ; benzotriazole‐hydrazone hybrid 50 (IC 50 : 25 nM, SRB assay) was 18‐fold more potent than doxorubicin (IC 50 : 450 nM) against HL‐60 leukemia cells, and this hybrid accumulated cells in pre‐G1 phase, arrested cell cycle at G2/M phase and induced apoptosis [ 110 ] ; 1,2,3‐triazole‐10,11‐dihydro‐9 H ‐9,10‐[3,4]epipyrroloanthracene‐12,14(13 H ,15 H )‐dione hybrid 51 (IC 50 : 4.8 and 1.0 μM, MTT assay) showed promising activity against HL‐60 and its multidrug‐resistant counterpart HL60R cells, demonstrating its potential to overcome drug resistance.…”