Aryl Quinazolinone Derivatives as Novel Therapeutic Agents against Brain-Eating Amoebae

被引:19
作者
Mungroo, Mohammad Ridwane [2 ]
Shahbaz, Muhammad Saquib [3 ]
Anwar, Ayaz [3 ]
Saad, Syed Muhammad [3 ]
Khan, Khalid Mohammed [3 ]
Khan, Naveed Ahmed [1 ]
Siddiqui, Ruqaiyyah [2 ]
机构
[1] Amer Univ Sharjah, Sharjah, U Arab Emirates
[2] Sunway Univ, Bandar Sunway, Malaysia
[3] Univ Karachi, Karachi, Pakistan
来源
ACS CHEMICAL NEUROSCIENCE | 2020年 / 11卷 / 16期
关键词
Brain-eating amoeba; antiamoebic; medicinal chemistry; quinazolinone; nanoparticles; ANTIMICROBIAL ACTIVITY; BIOLOGICAL EVALUATION; CYTOTOXIC EVALUATION; MOLECULAR DOCKING; ANTIBACTERIAL; ANTIFUNGAL; DESIGN;
D O I
10.1021/acschemneuro.9b00596
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
Naegleria fowleri and Balamuthia mandrillaris are protist pathogens that infect the central nervous system, causing primary amoebic meningoencephalitis and granulomatous amoebic encephalitis with mortality rates of over 95%. Quinazolinones and their derivatives possess a wide spectrum of biological properties, but their antiamoebic effects against brain-eating amoebae have never been tested before. In this study, we synthesized a variety of 34 novel arylquinazolinones derivatives (Q1-Q34) by altering both quinazolinone core and aryl substituents. To study the antiamoebic activity of these synthetic arylquinazolinones, amoebicidal and amoebistatic assays were performed against N. fowleri and B. mandrillaris. Moreover, amoebae-mediated host cells cytotopathogenicity and cytotoxicity assays were performed against human keratinocytes cells in vitro. The results revealed that selected arylquinazolinones derivatives decreased the viability of B. mandrillaris and N. fowleri significantly (P < 0.05) and reduced cytopathogenicity of both parasites. Furthermore, these compounds were also found to be least cytotoxic against HaCat cells. Considering that nanoparticle-based materials possess potent in vitro activity against brain-eating amoebae, we conjugated quinazolinones derivatives with silver nanoparticles and showed that activities of the drugs were enhanced successfully after conjugation. The current study suggests that quinazolinones alone as well as conjugated with silver nanoparticles may serve as potent therapeutics against brain-eating amoebae.
引用
收藏
页码:2438 / 2449
页数:12
相关论文
共 40 条
  • [1] Synthesis and Biological Evaluation of a Novel Series of 6,8-Dibromo-4(3H)quinazolinone Derivatives as Anticancer Agents
    Ahmed, Marwa F.
    Youns, Mahmoud
    [J]. ARCHIV DER PHARMAZIE, 2013, 346 (08) : 610 - 617
  • [2] Antioxidant and antimicrobial activities of novel quinazolinones
    Al-Amiery, Ahmed A.
    Kadhum, Abdul Amir H.
    Shamel, Mohammed
    Satar, Mustafa
    Khalid, Yehiah
    Mohamad, Abu Bakar
    [J]. MEDICINAL CHEMISTRY RESEARCH, 2014, 23 (01) : 236 - 242
  • [3] Novel antiacanthamoebic compounds belonging to quinazolinones
    Anwar, Ayaz
    Shahbaz, Muhammad Saquib
    Saad, Syed Muhammad
    Kanwal
    Khan, Khalid Mohammed
    Siddiqui, Rugaiyyah
    Khan, Naveed Ahmed
    [J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2019, 182
  • [4] Comparison of antibacterial activity of Ag nanoparticles synthesized from leaf extract of Parthenium hystrophorus L in aqueous media and Gentamicin sulphate: in-vitro
    Anwar, Mohammad F.
    Yadav, Deepak
    Kapoor, Sumeet
    Chander, Jagdish
    Samim, Mohd.
    [J]. DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 2015, 41 (01) : 43 - 50
  • [5] The effect of different environmental conditions on the encystation of Acanthamoeba castellanii belonging to the T4 genotype
    Aqeel, Yousuf
    Siddiqui, Ruqaiyyah
    Iftikhar, Hira
    Khan, Naveed Ahmed
    [J]. EXPERIMENTAL PARASITOLOGY, 2013, 135 (01) : 30 - 35
  • [6] Principles of nanoparticle design for overcoming biological barriers to drug delivery
    Blanco, Elvin
    Shen, Haifa
    Ferrari, Mauro
    [J]. NATURE BIOTECHNOLOGY, 2015, 33 (09) : 941 - 951
  • [7] Synthesis, 2D-QSAR Studies and Biological Evaluation of Quinazoline Derivatives as Potent Anti-Trypanosoma cruzi Agents
    Bollini, Maricla
    Bruno, Ana M.
    Nino, Maria E.
    Casal, Juan J.
    Sasiambarrena, Leandro D.
    Valdez, Damian A. G.
    Battini, Leandro
    Puente, Vanesa R.
    Lombardo, Maria E.
    [J]. MEDICINAL CHEMISTRY, 2019, 15 (03) : 265 - 276
  • [8] Identification of novel quinazoline derivatives as potent antiplasmodial agents
    Bouchut, Anne
    Rotili, Dante
    Pierrot, Christine
    Valente, Sergio
    Lafitte, Sophia
    Schultz, Johan
    Hoglund, Urban
    Mazzone, Roberta
    Lucidi, Alessia
    Fabrizi, Giancarlo
    Pechalrieu, Dany
    Arimondo, Paola B.
    Skinner-Adams, Tina S.
    Chua, Ming Jang
    Andrews, Kathy T.
    Mai, Antonello
    Khalife, Jamal
    [J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2019, 161 : 277 - 291
  • [9] One-pot, multicomponent synthesis of 2,3-disubstituted quinazolin-ones with potent and selective activity against Toxoplasma gondii
    Brown, Carla E.
    Kong, Tiffany
    Bordon, Claudia
    Yolken, Robert
    Jones-Brando, Lorraine
    McNulty, James
    [J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2018, 28 (09) : 1642 - 1646
  • [10] De Jonckheere JF, 2002, ACTA PROTOZOOL, V41, P309