PMID- 32698741
OWN - NLM
STAT- MEDLINE
DCOM- 20211230
LR  - 20211230
IS  - 1875-5992 (Electronic)
IS  - 1871-5206 (Linking)
VI  - 21
IP  - 9
DP  - 2021
TI  - New Hybrid Scaffolds Based on Carbazole-Chalcones as Potent Anticancer Agents.
PG  - 1082-1091
LID - 10.2174/1871520620666200721110732 [doi]
AB  - BACKGROUND AND OBJECTIVES: Despite various technological advances for the 
      treatment of cancer, the identification of new chemical entities with potent 
      anticancer effects remain an indispensable requirement of the time due to 
      multi-drug resistance exhibited by previously developed anticancer drugs. 
      Particularly, the hybrid drugs incorporating two individual bioactive 
      pharmacophores present medicinally important structural leads, thus improving the 
      pharmacodynamic profile of the drug molecules. The antiproliferative and 
      pro-apoptotic activity of the carbazole-chalcone hybrids on human breast and 
      cervical cancer cells will be examined. MATERIALS AND METHODS: To overcome such 
      complications, in the current study, we evaluated the cytotoxic effects of 
      carbazole-chalcone hybrids on human breast adenocarcinoma (MCF-7), cervical 
      adenocarcinoma (HeLa) cells and normal cells, i.e., Baby Hamster Kidney cells 
      (BHK-21) using MTT (dimethyl-2-thiazolyl-2,5- diphenyl-2H-tetrazolium bromide) 
      assay. The mechanistic studies were performed on potent compound 4g by 
      fluorescent microscopic studies, release of Lactate Dehydrogenase (LDH) and 
      mitochondrial membrane potential, activation of caspase-9 and -3 and flow 
      cytometric analysis. RESULTS: As revealed by MTT assay, compound 4g was 
      identified as the most potent derivative among the tested series with IC(50) 
      values of 5.64 and 29.15muM against HeLa and MCF-7 cells, respectively. The 
      results were compared with cisplatin. Fluorescent microscopic studies using 
      4',6-diamidino-2-phenylindole (DAPI) and Propidium Iodide (PI) staining confirmed 
      the occurrence of apoptosis in HeLa cells treated with the most active compound 
      4g. Moreover, compound 4g also triggered the release of Lactate Dehydrogenase 
      (LDH) in treated HeLa and MCF-7 cells while a fluorescence assay displayed a 
      remarkable increase in the activity of caspase-9 and -3. Moreover, flow 
      cytometric results revealed that compound 4g caused G(0)/G(1) arrest in the 
      treated HeLa cells. CONCLUSION: Our results demonstrated that the compound 4g 
      possesses chemotherapeutic properties against breast cancer and cervical 
      adenocarcinoma cells, thus warranting further research to test the anticancer 
      potential of this compound at preclinical and clinical level.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Rashid, Faisal
AU  - Rashid F
AD  - Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad 
      Campus, Abbottabad-22060, Pakistan.
FAU - Zaib, Sumera
AU  - Zaib S
AD  - Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad 
      Campus, Abbottabad-22060, Pakistan.
FAU - Ibrar, Aliya
AU  - Ibrar A
AD  - Department of Chemistry, Faculty of Science, The University of Haripur, Haripur, 
      KPK-22620, Pakistan.
FAU - Ejaz, Syeda A
AU  - Ejaz SA
AD  - Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad 
      Campus, Abbottabad-22060, Pakistan.
FAU - Saeed, Aamer
AU  - Saeed A
AD  - Department of Chemistry, Quaid-i-Azam University, Islamabad-45320, Pakistan.
FAU - Iqbal, Jamshed
AU  - Iqbal J
AD  - Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad 
      Campus, Abbottabad-22060, Pakistan.
FAU - Khan, Imtiaz
AU  - Khan I
AD  - Department of Chemistry and Manchester Institute of Biotechnology, The University 
      of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Anticancer Agents Med Chem
JT  - Anti-cancer agents in medicinal chemistry
JID - 101265649
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Carbazoles)
RN  - 0 (Chalcones)
RN  - 0P2197HHHN (carbazole)
SB  - IM
MH  - Antineoplastic Agents/chemical synthesis/chemistry/*pharmacology
MH  - Apoptosis/drug effects
MH  - Carbazoles/chemistry/*pharmacology
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chalcones/chemistry/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Screening Assays, Antitumor
MH  - Humans
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Molecular Structure
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - 4'
OT  - 6-diamidino-2-phenylindole (DAPI)
OT  - Carbazole-chalcone hybrids
OT  - HeLa cells
OT  - MCF-7
OT  - caspase-3
OT  - caspase-9
OT  - flow cytometry
OT  - lactate dehydrogenase
EDAT- 2020/07/24 06:00
MHDA- 2021/12/31 06:00
CRDT- 2020/07/24 06:00
PHST- 2020/04/15 00:00 [received]
PHST- 2020/06/25 00:00 [revised]
PHST- 2020/06/30 00:00 [accepted]
PHST- 2020/07/24 06:00 [pubmed]
PHST- 2021/12/31 06:00 [medline]
PHST- 2020/07/24 06:00 [entrez]
AID - ACAMC-EPUB-108366 [pii]
AID - 10.2174/1871520620666200721110732 [doi]
PST - ppublish
SO  - Anticancer Agents Med Chem. 2021;21(9):1082-1091. doi: 
      10.2174/1871520620666200721110732.