본문 바로가기
HOME> 논문 > 논문 검색상세

논문 상세정보

European journal of medicinal chemistry v.143, 2018년, pp.1373 - 1386   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Synthesis, monoamine oxidase inhibition activity and molecular docking studies of novel 4-hydroxy-N′-[benzylidene or 1-phenylethylidene]-2-H/methyl/benzyl-1,2-benzothiazine-3-carbohydrazide 1,1-dioxides

Saddique, Furqan Ahmad (Department of Chemistry, Government College University, Faisalabad, 38000, Pakistan ) ; Zaib, Sumera (Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad, 22060, Pakistan ) ; Jalil, Saquib (Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad, 22060, Pakistan ) ; Aslam, Sana (Department of Chemistry, Government College Women University, Faisalabad, 38000, Pakistan ) ; Ahmad, Matloob (Department of Chemistry, Government College University, Faisalabad, 38000, Pakistan ) ; Sultan, Sadia (Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia ) ; Naz, Humera (Faculty of Pharmacy, Universiti Teknologi MARA, Puncak Alam Campus, 42300 Bandar Puncak Alam, Selangor Darul Ehsan, Malaysia ) ; Iqbal, Mazhar (Drug Discovery and Structural Biology Group, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering, Faisalabad 38000, Pakistan ) ; Iqbal, Jamshed (Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad, 220 ) ;
  • 초록  

    Abstract Three series of 4-hydroxy- N ′ -[benzylidene/1-phenylethylidene]-2- H /methyl/benzyl-1,2-benzothiazine-3-carbohydrazide 1,1-dioxides (9–11)a-l were synthesized and unraveled to be highly potent dual inhibitors of monoamine oxidases (MAO-A and MAO-B). All the examined compounds demonstrated IC 50 values in lower micro-molar range for both MAO-A as well as MAO-B. The most active MAO-A inhibitor was 4-hydroxy- N′ -(1-phenylethylidene)-2 H -benzo[ e ][1,2]thiazine-3-carbohydrazide 1,1-dioxide ( 9i ) with an IC 50 value of 0.11 ± 0.005 μM, whereas, methyl 4-hydroxy-2 H -benzo[ e ][1,2]thiazine-3-carboxylate 1,1-dioxide ( 3 ) was the most active MAO-B inhibitor with an IC 50 value of 0.21 ± 0.01 μM. Enzyme kinetics studies revealed that the most potent compounds inhibited both MAO enzymes (A & B) in a competitive fashion. Molecular docking studies were also performed to obtain an intuitive picture of inhibition potential for potent inhibitors. The high potency of these compounds is optimally combined with highly favorable ADME profile with predicted good oral bioavailability. Highlights Three series of benzothiazine-3-carbohydrazide were synthesized. Potent inhibitors of monoamine oxidases were unraveled. Kinetics studies were carried out for potent inhibitors of MAO-A & MAO-B. Molecular docking studies further supported the in vitro results. Compounds exhibited favorable ADME profile with good oral bioavailability. Graphical abstract [DISPLAY OMISSION]


  • 주제어

    Benzothiazine .   Monoamine oxidase .   Molecular docking .   Bioavailability.  

 활용도 분석

  • 상세보기

    amChart 영역
  • 원문보기

    amChart 영역

원문보기

무료다운로드
  • 원문이 없습니다.

유료 다운로드의 경우 해당 사이트의 정책에 따라 신규 회원가입, 로그인, 유료 구매 등이 필요할 수 있습니다. 해당 사이트에서 발생하는 귀하의 모든 정보활동은 NDSL의 서비스 정책과 무관합니다.

원문복사신청을 하시면, 일부 해외 인쇄학술지의 경우 외국학술지지원센터(FRIC)에서
무료 원문복사 서비스를 제공합니다.

NDSL에서는 해당 원문을 복사서비스하고 있습니다. 위의 원문복사신청 또는 장바구니 담기를 통하여 원문복사서비스 이용이 가능합니다.

이 논문과 함께 출판된 논문 + 더보기