Synthesis and Evaluation of Novel DNA Minor Groove Binders as Antiamoebic Agents

被引:10
|
作者
Alniss, Hasan Y. [1 ,2 ]
Khan, Naveed A. [3 ]
Boghossian, Anania [4 ]
Akbar, Noor [3 ]
Al-Jubeh, Hadeel M. [2 ]
Msallam, Yousef A. [1 ,2 ]
Saeed, Balsam Q. [3 ]
Siddiqui, Ruqaiyyah [4 ]
机构
[1] Univ Sharjah, Coll Pharm, POB 27272, Sharjah, U Arab Emirates
[2] Univ Sharjah, Sharjah Inst Med Res, POB 27272, Sharjah, U Arab Emirates
[3] Univ Sharjah, Coll Med, Dept Clin Sci, POB 27272, Sharjah, U Arab Emirates
[4] Amer Univ Sharjah, Coll Arts & Sci, POB 26666, Sharjah, U Arab Emirates
来源
ANTIBIOTICS-BASEL | 2022年 / 11卷 / 07期
关键词
Acanthamoeba castellanii; trophozoites; cysts; sight-threatening; DNA minor groove binders; distamycin analogues; organic synthesis; MOLECULAR RECOGNITION; BINDING;
D O I
10.3390/antibiotics11070935
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
The free-living amoeba Acanthamoeba castellanii is responsible for the central nervous infection granulomatous amoebic encephalitis and sight-threatening infection Acanthamoeba keratitis. Moreover, no effective treatment is currently present, and a combination drug therapy is used. In this study, twelve DNA minor groove binders (MGBs) were synthesized and tested for their antiamoebic activity via amoebicidal, encystation, excystation, and cytopathogenicity assays. It was found that the compounds MGB3, MGB6, MGB22, MGB24, and MGB16 significantly reduce amoeba viability to 76.20%, 59.45%, 66.5%, 39.32%, and 43.21%, respectively, in amoebicidal assays. Moreover, the compounds MGB6, MGB20, MGB22, MGB28, MGB30, MGB32, and MGB16 significantly inhibit Acanthamoeba cysts, leading to the development of only 46.3%, 39%, 30.3%, 29.6%, 27.8%, 41.5%, and 45.6% cysts. Additionally, the compounds MGB3, MGB4, MGB6, MGB22, MGB24, MGB28, MGB32, and MGB16 significantly reduce the re-emergence of cysts to trophozoites, with viable trophozoites being only 64.3%, 47.3%, 41.4%, 52.9%, 55.4%, 40.6%, 62.1%, and 51.7%. Moreover, the compounds MGB3, MGB4, and MGB6 exhibited the greatest reduction in amoeba-mediated host-cell death, with cell death reduced to 41.5%, 49.4%, and 49.5%. With the following determined, future in vivo studies can be carried out to understand the effect of the compounds on animal models such as mice.
引用
收藏
页数:27
相关论文
共 50 条
  • [1] Aromatic analogues of DNA minor groove binders - synthesis and biological evaluation
    Puckowska, A
    Bielawski, K
    Bielawski, A
    Midura-Nowaczek, K
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2004, 39 (01) : 99 - 105
  • [2] Synthesis, biological evaluation, and modeling of dimeric PPI analogues as novel DNA minor groove binders
    Yang, Yan-Hui
    Wang, Qing-He
    Nie, Han
    Chen, Hong
    Cheng, Mao-Sheng
    MOLECULES, 2008, 13 (05): : 1179 - 1188
  • [3] DNA minor groove binders as potential antitumor and antimicrobial agents
    Baraldi, PG
    Bovero, A
    Fruttarolo, F
    Preti, D
    Tabrizi, MA
    Pavani, MG
    Romagnoli, R
    MEDICINAL RESEARCH REVIEWS, 2004, 24 (04) : 475 - 528
  • [4] DNA MINOR GROOVE BINDERS
    MARKY, LA
    FERRANTE, R
    BRESLAUER, KJ
    BIOPHYSICAL JOURNAL, 1986, 49 (02) : A303 - A303
  • [5] DNA minor groove binders: Back in the groove
    Cai, Xuemei
    Gray, Phillip J., Jr.
    Von Hoff, Daniel D.
    CANCER TREATMENT REVIEWS, 2009, 35 (05) : 437 - 450
  • [6] Novel aromatic dications as DNA minor-groove binders
    Nagle, Padraic S.
    Kahvedzic, Amila
    McKeever, Catriona
    O'Donovan, Daniel H.
    Cordeiro, Alessandra
    Quinn, Susan J.
    Kelly, John M.
    Rozas, Isabel
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2009, 238
  • [7] Sugar-Oligoamides: Synthesis of DNA Minor Groove Binders
    Badia, Concepcion
    Souard, Florence
    Vicent, Cristina
    JOURNAL OF ORGANIC CHEMISTRY, 2012, 77 (23): : 10870 - 10881
  • [8] Synthesis and biological activity of benzamide DNA minor groove binders
    Khan, Gul Shahzada
    Pilkington, Lisa I.
    Barker, David
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (03) : 804 - 808
  • [9] Thermodynamics of DNA Minor Groove Binders
    Alniss, Hasan Y.
    JOURNAL OF MEDICINAL CHEMISTRY, 2019, 62 (02) : 385 - 402
  • [10] Conjugates of minor groove DNA binders with oligodeoxynucleotides: Synthesis and properties
    Levina, AS
    Metelev, VG
    Cohen, AS
    Zamecnik, PC
    ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT, 1996, 6 (02): : 75 - 85