TY - JOUR
T1 - Hydrazide-integrated carbazoles
T2 - Synthesis, computational, anticancer and molecular docking studies
AU - Krishnan, Kannan Gokula
AU - Ashothai, Pathinettampadi
AU - Padmavathy, Krishnaraj
AU - Lim, Wei-Meng
AU - Mai, Chun-Wai
AU - Thanikachalam, Punniyakoti V.
AU - Ramalingan, Chennan
N1 - Funding Information:
Financial assistance provided by the Indian Council of Medical Research, New Delhi (No. 58/16/2013BMS) and Kalasalingam Academy of Research and Education (PDF to KG) is gratefully acknowledged.
Publisher Copyright:
© 2019 The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.
PY - 2019/8/14
Y1 - 2019/8/14
N2 - A new class of carbazole-based hydrazides 6a-c, synthesized from carbazole by employing a multistep synthetic strategy, has been described. Detailed insight into their structures (6a-c) has been elucidated by UV-Vis, FT-IR and NMR (1H and 13C) spectroscopic studies. Theoretical investigation of the molecules 6a-c has been accomplished utilizing DFT and TD-DFT techniques with the B3LYP/6-311++G(d,p) method. Theoretical findings such as optimized structural, vibrational, and electronic properties, and proton and carbon chemical shifts of the targets 6a-c are in harmony with their experimental results and/or structurally related reported ones. Cytotoxicity of the target hydrazides 6a-c has been evaluated using human pancreatic cancer cells (AsPC1 and SW1990). The hydrazides 6a-c displayed a significant in vitro cytotoxic effect against both the pancreatic cancer cells AsPC1 (concentration that inhibits 50% cell viability, IC50: 3.42 ± 0.41 μM for 6a) and SW1990 (IC50: 22.42 ± 1.40 μM for 6a). The superior binding energy resulting from the in silico molecular docking approach of the hydrazide 6a indicates its greater affinity towards the receptor (binding energy: -8.63 kcal mol-1 and IC50: 475.05 nM). Thus, the hydrazide 6a could serve as a new lead for the development of anticancer agents.
AB - A new class of carbazole-based hydrazides 6a-c, synthesized from carbazole by employing a multistep synthetic strategy, has been described. Detailed insight into their structures (6a-c) has been elucidated by UV-Vis, FT-IR and NMR (1H and 13C) spectroscopic studies. Theoretical investigation of the molecules 6a-c has been accomplished utilizing DFT and TD-DFT techniques with the B3LYP/6-311++G(d,p) method. Theoretical findings such as optimized structural, vibrational, and electronic properties, and proton and carbon chemical shifts of the targets 6a-c are in harmony with their experimental results and/or structurally related reported ones. Cytotoxicity of the target hydrazides 6a-c has been evaluated using human pancreatic cancer cells (AsPC1 and SW1990). The hydrazides 6a-c displayed a significant in vitro cytotoxic effect against both the pancreatic cancer cells AsPC1 (concentration that inhibits 50% cell viability, IC50: 3.42 ± 0.41 μM for 6a) and SW1990 (IC50: 22.42 ± 1.40 μM for 6a). The superior binding energy resulting from the in silico molecular docking approach of the hydrazide 6a indicates its greater affinity towards the receptor (binding energy: -8.63 kcal mol-1 and IC50: 475.05 nM). Thus, the hydrazide 6a could serve as a new lead for the development of anticancer agents.
UR - https://www.scopus.com/pages/publications/85070062006
U2 - 10.1039/c9nj01912j
DO - 10.1039/c9nj01912j
M3 - Article
AN - SCOPUS:85070062006
SN - 1144-0546
VL - 43
SP - 12069
EP - 12077
JO - New Journal of Chemistry
JF - New Journal of Chemistry
IS - 30
ER -
