Evaluation of Rapanone and Nectandrin B as novel inhibitors for targeting the metastatic regulator protein BACH1 using breast cancer cell line Mcf-7

被引:2
作者
Arunachalam, Abirami [1 ]
Sankar, Muthumanickam [2 ]
Pandi, Boomi [2 ]
Paul, Soumi [1 ]
Thilagar, Sivasudha [1 ,3 ]
机构
[1] Bharathidasan Univ, Sch Environm Sci, Dept Environm Biotechnol, Tiruchirappalli 620024, Tamil Nadu, India
[2] Alagappa Univ, Dept Bioinformat, Karaikkudi, Tamil Nadu, India
[3] Bharathidasan Univ, Dept Environm Biotechnol, Tiruchirappalli 620024, Tamil Nadu, India
关键词
Transcription factor; BACH1; bioactive compounds; docking; molecular dynamics; drug discovery; MOLECULAR DOCKING; BTB DOMAIN; DYNAMICS;
D O I
10.1080/07391102.2023.2260880
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cancer formation is defined as the unrestrained proliferation of cells due to various factors acting as a causing agent. A limited number of over-expressed transcription factors are contributed to the development of numerous types of cancer. The metastatic regulator protein BTB And CNC Homology 1 (BACH1) is Cap 'N' Collar (CNC) and it belongs to a basic region leucine zipper (bZIP) family. The presence of the least level concentration of intracellular heme BACH1 forms heterodimers with musculo aponeurotic fibrosarcoma (sMAF) proteins and inhibits or induces the target gene expression. Based on the previous studies, BACH1 plays a critical player in the conditions of senescence and oxidative stress, cycling of cell life, heme degradation pathway and cancer, especially in metastasis. Discovering new anti-cancer drugs (identification of bioactive compounds) stages finally needs to inhibit the target protein. This present study is aimed to screen and identify stability, binding affinity and analysis of pharmacokinetics of selected compounds through structural screening, ADMET, DFT and MESP. From this study, it is revealed that Rapanone and Nectandrin B have the potential to alter the degree of gene expression via binding with the BACH1 allosteric region which will further change the degree of expression of BACH1 downstream target genes involved in the regulation of cancer progression particularly in metastasis. The two plant origin compounds Rapanone and Nectandrin B might be novel candidates for developing anti-cancer drugs. The predicted compounds were further validated through in-vitro experimental approaches.Communicated by Ramaswamy H. Sarma.
引用
收藏
页码:11185 / 11200
页数:16
相关论文
共 35 条
[1]   Identification of anti-filarial leads against aspartate semialdehyde dehydrogenase of Wolbachia endosymbiont of Brugia malayi: combined molecular docking and molecular dynamics approaches [J].
Amala, Mathimaran ;
Rajamanikandan, Sundaraj ;
Prabhu, Dhamodharan ;
Surekha, Kanagarajan ;
Jeyakanthan, Jeyaraman .
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2019, 37 (02) :394-410
[2]   TPGS-mediated one-pot synthesis, XRD structural analysis, antimicrobial evaluation and molecular docking of novel heterocycles as potential inhibitors of p53-MDM2 protein [J].
Anand, K. ;
Naicker, Tricia ;
Baijnath, Sooraj ;
Mphahlele, Malose J. ;
Katari, Naresh Kumar ;
Zamisa, Sizwe J. ;
Balakumar, C. ;
Vijayakumar, K. ;
Palanisamy, Subramanian ;
Saravanan, Muthupandian ;
Boomi, P. ;
Chuturgoon, Anil .
JOURNAL OF MOLECULAR STRUCTURE, 2020, 1202
[3]   Regulatory mechanisms of heme regulatory protein BACH1: a potential therapeutic target for cancer [J].
Arunachalam, Abirami ;
Lakshmanan, Dinesh Kumar ;
Ravichandran, Guna ;
Paul, Soumi ;
Manickam, Sivakumar ;
Kumar, Palanirajan Vijayaraj ;
Thilagar, Sivasudha .
MEDICAL ONCOLOGY, 2021, 38 (10)
[4]   Targeting transcription factors in cancer - from undruggable to reality [J].
Bushweller, John H. .
NATURE REVIEWS CANCER, 2019, 19 (11) :611-624
[5]   Identification of Thiourea-Based Inhibitors of the B-Cell Lymphoma 6 BTB Domain via NMR-Based Fragment Screening and Computer-Aided Drug Design [J].
Cheng, Huimin ;
Linhares, Brian M. ;
Yu, Wenbo ;
Cardenas, Mariano G. ;
Ai, Yong ;
Jiang, Wenjuan ;
Winkler, Alyssa ;
Cohen, Sandra ;
Melnick, Ari ;
MacKerell, Alexander, Jr. ;
Cierpicki, Tomasz ;
Xue, Fengtian .
JOURNAL OF MEDICINAL CHEMISTRY, 2018, 61 (17) :7573-7588
[6]   Promising phytochemicals of traditional Indian herbal steam inhalation therapy to combat COVID-19-An in silico study [J].
Gowrishankar, Shanmugaraj ;
Muthumanickam, Sankar ;
Kamaladevi, Arumugam ;
Karthika, Chandrasekar ;
Jothi, Ravi ;
Boomi, Pandi ;
Maniazhagu, Dharuman ;
Pandian, Shunmugiah Karutha .
FOOD AND CHEMICAL TOXICOLOGY, 2021, 148
[7]   Synthesis, molecular docking, molecular dynamic, quantum calculation, and antibacterial activity of new Schiff base-metal complexes [J].
Hashem, Heba E. ;
Nath, Ashutosh ;
Kumer, Ajoy .
JOURNAL OF MOLECULAR STRUCTURE, 2022, 1250
[8]   Synthesis of 5, 6-diaroylisoindoline-1, 3-dione and computational approaches for investigation on structural and mechanistic insights by DFT [J].
Hoque, Mohammad Mazharol ;
Hussen, Md Sajib ;
Kumer, Ajoy ;
Khan, Md Wahab .
MOLECULAR SIMULATION, 2020, 46 (16) :1298-1307
[9]   Anti-HCV and anti-malaria agent, potential candidates to repurpose for coronavirus infection: Virtual screening, molecular docking, and molecular dynamics simulation study [J].
Hosseini, Faezeh Sadat ;
Amanlou, Massoud .
LIFE SCIENCES, 2020, 258
[10]   Plant derived anticancer agents: A green approach towards skin cancers [J].
Ijaz, Shakeel ;
Akhtar, Naveed ;
Khan, Muhammad Shoaib ;
Hameed, Abdul ;
Irfan, Muhammad ;
Arshad, Muhammad Adeel ;
Ali, Sajid ;
Asrar, Muhammad .
BIOMEDICINE & PHARMACOTHERAPY, 2018, 103 :1643-1651