Design, Synthesis, In-silico and Cytotoxic Studies of Indole Derivatives as Potent BCL-2 inhibitors

被引:0
|
作者
Etnoori, Sharada [1 ]
Barothu, Raju [1 ]
Chilakala, Nagendra babu [1 ]
Veldurthi, Shashikala [1 ,2 ]
Kokku, Premalatha [1 ,2 ]
机构
[1] Osmania Univ, Dept Chem, Hyderabad 500007, Telangana, India
[2] Telangana Mahila Viswavidyalayam, Hyderabad 500095, Telangana, India
关键词
Indole; InCl3; Solvent free conditions; In silico modeling; BCL-2; protein; Anticancer activity; ANTICANCER; HYBRIDS; FAMILY;
D O I
10.13005/ojc/400519
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
Indole-based compounds have emerged as a potentially game-changing category of molecules that specifically target Bcell lymphoma-2 (BCL-2) protein, offering an innovative approach to the management of breast cancer. Breast cancer is a major public health concern globally, necessitating continued research into innovative therapeutic approaches. One such strategy involves inhibiting (BCL-2) protein, which is overexpressed in cancer cells and inhibits apoptosis. A series of indole derivatives (b1-b12) were synthesized using indium chloride as a catalyst in a solvent free conditions to investigate their potential to interfere with BCL-2 mediated survival pathways. Additionally, In silico modeling was employed to identify novel BCL-2 inhibitors and made structural alterations to enhance the selectivity and potency of indole compounds. The efficacy of indole derivatives was determined using an In vitro model that utilizes the MCF cell line. The findings obtained demonstrated that the compound b11 possessed a considerable amount of anticancer activity.
引用
收藏
页码:1367 / 1376
页数:10
相关论文
共 50 条
  • [31] Design and synthesis of benzimidazole derivatives as apoptosis-inducing agents by targeting Bcl-2 protein
    Ilhan, Suleyman
    Camli Pulat, Cisil
    Oguz, Ferdi
    Bektas, Hakan
    Mentese, Emre
    Atmaca, Harika
    MOLECULAR DIVERSITY, 2023, 27 (04) : 1703 - 1712
  • [32] Hybrid In Silico and TR-FRET-Guided Discovery of Novel BCL-2 Inhibitors
    Sahin, Kader
    Orhan, Muge Didem
    Avsar, Timucin
    Durdagi, Serdar
    ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE, 2021, 4 (03) : 1111 - 1123
  • [33] Design, synthesis, in vitro, and in silico studies of new thiadiazol derivatives as promising VEGFR-2 inhibitors and apoptosis inducers
    Mahdy, Hazem A.
    Elkady, Hazem
    Elgammal, Walid E.
    Elkaeed, Eslam B.
    Alsfouk, Aisha A.
    Ibrahim, Ibrahim M.
    Husein, Dalal Z.
    Elkady, Mohamed A.
    Metwaly, Ahmed M.
    Eissa, Ibrahim H.
    JOURNAL OF MOLECULAR STRUCTURE, 2024, 1316
  • [34] Design, Synthesis and Docking Studies of New Indazole Derivatives as Potent Cytotoxic and Antibacterial Agents
    Reddy, Ganji Sreekanth
    Viswanath, I. V. Kasi
    Rao, Allaka Tejeswara
    INDIAN JOURNAL OF HETEROCYCLIC CHEMISTRY, 2018, 28 (04) : 467 - 475
  • [35] 1-Phenyl-1H-indole derivatives as a new class of Bcl-2/Mcl-1 dual inhibitors: Design, synthesis, and preliminary biological evaluation
    Xu, Guangsen
    Liu, Tingting
    Zhou, Yi
    Yang, Xinying
    Fang, Hao
    BIOORGANIC & MEDICINAL CHEMISTRY, 2017, 25 (20) : 5548 - 5556
  • [36] Synthesis, investigation of biological effects and in silico studies of new benzimidazole derivatives as aromatase inhibitors
    Saglik, Begum Nurpelin
    Sen, Ahmet Mucahit
    Evren, Asaf Evrim
    Cevik, Ulviye Acar
    Osmaniye, Derya
    Cavusoglu, Betul Kaya
    Levent, Serkan
    Karaduman, Abdullah Burak
    Ozkay, Yusuf
    Kaplancikli, Zafer Asim
    ZEITSCHRIFT FUR NATURFORSCHUNG SECTION C-A JOURNAL OF BIOSCIENCES, 2020, 75 (9-10): : 353 - 362
  • [37] Structure-Based Design of Potent Bcl-2/Bcl-xL Inhibitors with Strong in Vivo Antitumor Activity
    Zhou, Haibin
    Aguilar, Angelo
    Chen, Jianfang
    Bai, Longchuan
    Liu, Liu
    Meagher, Jennifer L.
    Yang, Chao-Yie
    McEachern, Donna
    Cong, Xin
    Stuckey, Jeanne A.
    Wang, Shaomeng
    JOURNAL OF MEDICINAL CHEMISTRY, 2012, 55 (13) : 6149 - 6161
  • [38] Design, synthesis, and evaluation of novel thiadiazole derivatives as potent VEGFR-2 inhibitors: a comprehensive in vitro and in silico study
    Eissa, Ibrahim H.
    Elgammal, Walid E.
    Mahdy, Hazem A.
    Zara, Susi
    Carradori, Simone
    Husein, Dalal Z.
    Alharthi, Maymounah N.
    Ibrahim, Ibrahim M.
    Elkaeed, Eslam B.
    Elkady, Hazem
    Metwaly, Ahmed M.
    RSC ADVANCES, 2024, 14 (48) : 35505 - 35519
  • [39] In silico and in vitro studies of thiosemicarbazone-indole hybrid compounds as potent α-glycosidase inhibitors
    Bakherad, Zohreh
    Bakherad, Hamid
    Sepehri, Saghi
    Faramarzi, Mohammad Ali
    Mahnam, Karim
    Mojtabavi, Somayeh
    Mahdavi, Mohammad
    COMPUTATIONAL BIOLOGY AND CHEMISTRY, 2022, 97
  • [40] Identification of new theobromine-based derivatives as potent VEGFR-2 inhibitors: design, semi-synthesis, biological evaluation, and in silico studies
    Eissa, Ibrahim H. H.
    Yousef, Reda G. G.
    Elkady, Hazem
    Elkaeed, Eslam B. B.
    Alsfouk, Aisha A. A.
    Husein, Dalal Z. Z.
    Ibrahim, Ibrahim M. M.
    Elhendawy, Mostafa A. A.
    Godfrey, Murrell
    Metwaly, Ahmed M. M.
    RSC ADVANCES, 2023, 13 (33) : 23285 - 23307