Novel 2,6-disubstituted pyridine hydrazones: Synthesis, anticancer activity, docking studies and effects on caspase-3-mediated apoptosis

Şenkardeş, Sevil; Türe, Aslı; Ekrek, Sedanur; Durak, Asım Tuğrul; Abbak, Mürüvvet; Çevik, Özge; Kaşkatepe, Banu; Küçükgüzel, İlkay; Küçükgüzel, Ş. Güniz

doi:10.1016/j.molstruc.2020.128962

Cited by 26 publications

(19 citation statements)

References 38 publications

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“…In the cases of aromatic aldehydes-condensed N-acylhydrazones, 1 H-NMR spectra in DMSO-d 6 showed two peaks of the -CH 2 CO and CH-CH 3 groups that be attributed to the presence of two possible syn-anti isomers of the amide bond or E-Z isomer. For all the nal compounds, the protons of azomethine and amide resonated at the expected regions in the literature [13][14][15]23].…”

Section: Chemistrymentioning

confidence: 64%

“…Chemical shift (δ) values of rotameric hydrogens whenever identi ed are presented within parentheses by assigning an asterisk (*) along with that of other forms [28]. Compounds 1a-n and 2a-b are already recorded in the literature [4,[13][14][15][16][17][18][19][20][21]. Compounds 1i and its ester derivative, 3e and 3j have CAS Registry Numbers but no reference, analytical, or spectral data.…”

Section: Methodsmentioning

confidence: 99%

“…The synthesis route of hydrazides (1a-h and 1l-n) and semicarbazide (1k) is shown in Scheme 1. First, acid hydrazides (1a-h) were synthesized by re uxing corresponding esters and hydrazine hydrate in ethanol according to the reported method [4,[13][14][15][16][17]. The compounds (1i-j) were synthesized according to the previously reported procedure starting from benzocaine [18].…”

Section: Chemistrymentioning

confidence: 99%

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Synthesis and anticancer activity of novel hydrazone linkage-based aryl sulfonate derivatives as apoptosis inducers

et al. 2022

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In the present study, the various 28 hybrid molecules containing hydrazone and sulfonate moiety were synthesized and characterized by FTIR, 1 H-NMR, 13 C-NMR spectroscopy and LC-MS spectrometry, besides elemental analysis. The compounds were evaluated for their antiproliferative effects against six cancer cell lines, namely A549 (non-small cell lung cancer), MCF-7 (breast cancer), HT-29 (colorectal adenocarcinoma cancer), PC-3 (androgen-independent prostate adenocarcinoma), Hep3B (hepatocellular carcinoma cancer), and HeLa (epitheloid cervix carcinoma cancer). Among all the target compounds, compounds 4g and 4h exhibited more promising effects on MCF-7 cell lines (IC 50 =17.8 mM and 21.2 mM, respectively) with high selectivity. Further mechanistic studies proposed that compounds 4g and 4h induced apoptosis is mediated through the intrinsic apoptotic pathway with changes in mitochondrial membrane potential by nally activating caspase-9 and caspase-3. The results have been encouraging enough to merit further investigation.

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Section: Chemistrymentioning

confidence: 64%

Section: Methodsmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

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Synthesis and anticancer activity of novel hydrazone linkage-based aryl sulfonate derivatives as apoptosis inducers

et al. 2022

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“…Many caspase‐3 activation‐mediated apoptosis inducers for potential cytotoxicity have been reported till date (Jain et al., 2012, 2013, 2019; Jain, Pattnaik, et al., 2017; Kumar et al., 2021; Lv et al., 2020; Vaidya et al., 2020a, 2020b; Vaidya, Pathak, et al., 2020). Numerous SAR and QSAR studies were reported in favor to search of these compounds (Mansouri et al., 2020; Jain, Vaidya, et al., 2017; Şenkardeş et al., 2021; Vaidya et al., 2014). These caspase‐3 activators are described herein:…”

Section: Caspase‐3 Activatorsmentioning

confidence: 99%

Caspase‐3: A primary target for natural and synthetic compounds for cancer therapy

Yadav

Jain³

et al. 2021

Chem Biol Drug Des

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Caspases, a group of protease enzymes (cysteine proteases), exist as inactive zymogens in the cells and execute apoptosis (programmed cell death). Caspase‐3, an executioner caspase, plays an imperative role in apoptosis and becomes a primary target for cancer treatment. A number of analogues of quinazoline, quinazolinone, indoloquinazolines, quinone, naphthoquinones, pyrroloiminoquinones, styrylquinolines, tetheredtetrahydroquinoline, fluoroquinolone, thiosemicarbazones, benzotriazole, pyrimidines, chalcone, and carbazoles have been reported till date, representing caspase‐3 mediated apoptosis for cancer therapy. Simultaneously, plant isolates, including lysicamine, podophyllotoxin, and majoranolide, have also been claimed for caspase‐3‐mediated apoptosis‐induced cytotoxicity. Procaspase‐activating compound‐1 (PAC‐1) is the first FDA approved orphan drug, and its synthetic derivative WF‐208 also showed fascinating caspase‐3 mediated anticancer activity. Till date, a large number of compounds have been reported and patented for their caspase‐3‐mediated cytotoxicity and now scientist is also focusing to introduce new compounds in market to encompass anticancer activity.

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“…In recent years, screening studies on anticancer effects on new compounds containing hydrazidehydrazone have gained importance in order to accelerate the development of new more effective, less toxic chemotherapeutic agents [11][12][13][14][15][16][17][18]. Especially in this period when COX-2 enzyme is an important molecular targeting for anticancer therapies, etodolac (1,8-diethyl-1,3,4,9-tetrahydropyrano [3,4-b]indole-1-yl)acetic acid) has been reported to have anticancer activity against various prostate cancers; Compounds in the structure of hydrazone, which have also been reported in the literature, have been synthesized using etodolac active substance.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and anticancer activity against prostate cancer of hydrazide-hydrazones derived from etodolac

KOÇ¹,

ATLIHAN²,

Tiber³

et al. 2022

jrp

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diethyl-1,3,4,9-tetrahydrapyrano(3,4-b)indole-1-acetic acid] is a nonsteroidal antiinflammatory drug that contains carboxylic acid group with the structure of pyrano [3,4-b]indole. In this study, a series of novel (R,S)-Etodolac derivatives (3a-l) bearing hydrazide-hydrazone moiety were synthesized. The structures of these compounds were characterized by spectral ( 1 H-NMR and FT-IR analyses) methods. All synthesized compounds were screened for anticancer activity against androgen-independent prostate adenocarcinoma (PC-3, DU-145) and androgen-dependent prostate adenocarcinoma (LNCaP) cell lines by using WST-8 colorimetric method. This method was used for cell viability and cytotoxicity analysis. Compound 3b (SGK-720) [2-(1,8-diethyl-1,3,4,9tetrahydropyrano[3,4-b]indole-1-yl)acetic acid [(2,6-dichlorophenyl)methylene]hydrazides] showed 10.36, 5.24, 15.53 µM anticancer activity against PC3, DU145, LNCaP cancer cell lines, respectively. According to JC-1 mitochondrial membrane potential test and Annexin V/PI staining, 3b was found to have apoptotic effect on these cancer cells. It is concluded that compound 3b containing 2,6-dichloro substituents may be one of the candidate molecules to cope with prostate cancer.

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Novel 2,6-disubstituted pyridine hydrazones: Synthesis, anticancer activity, docking studies and effects on caspase-3-mediated apoptosis

Cited by 26 publications

References 38 publications

Synthesis and anticancer activity of novel hydrazone linkage-based aryl sulfonate derivatives as apoptosis inducers

Synthesis and anticancer activity of novel hydrazone linkage-based aryl sulfonate derivatives as apoptosis inducers

Caspase‐3: A primary target for natural and synthetic compounds for cancer therapy

Synthesis and anticancer activity against prostate cancer of hydrazide-hydrazones derived from etodolac

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