TY - JOUR
T1 - Cu-promoted synthesis of Indolo[2,3-b]quinoxaline-Mannich adducts via three-component reaction and their anti-proliferative evaluation on colorectal and ovarian cancer cells
AU - Chowdhary, Shefali
AU - Raza, Asif
AU - Seboletswe, Pule
AU - Cele, Nosipho
AU - Sharma, Arun K.
AU - Singh, Parvesh
AU - Kumar, Vipan
N1 - Funding Information:
UGC (NFSC) has been acknowledged for providing fellowship to SC (Ref No. 1594/CSIR-UGC NET DEC 2018). VK thanks Council of Scientific and Industrial Research (CSIR) for providing financial support (grant no. 02(0400)/21/EMR-II). AKS thanks the Department of Pharmacology, Penn State College of Medicine, and Penn State Cancer Institute for financial support. PS gratefully acknowledges the Centre for High-Performance Computing (CHPC), Cape Town (South Africa), for the supercomputing facilities. SC- synthesized and analysed the data; AR- conducted the biological studies; PS and NC- conducted docking studies; PS analysed computational data and finalized the draft; AS-analysed the biological data and finalized the draft; VK- conceptualized the work, compiled the data and finalized the draft.
Funding Information:
UGC (NFSC) has been acknowledged for providing fellowship to SC (Ref No. 1594/CSIR-UGC NET DEC 2018). VK thanks Council of Scientific and Industrial Research (CSIR) for providing financial support (grant no. 02(0400)/21/EMR-II ). AKS thanks the Department of Pharmacology, Penn State College of Medicine, and Penn State Cancer Institute for financial support. PS gratefully acknowledges the Centre for High-Performance Computing (CHPC), Cape Town (South Africa), for the supercomputing facilities.
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2023/3/5
Y1 - 2023/3/5
N2 - The present work intends to synthesize a new class of small molecules featuring the quinoxaline scaffold. The indolo [2,3-b]quinoxaline-Mannich adducts were designed, synthesized and their anticancer activities were tested using MTS assay against human ovarian cancer (OVCAR-3) and female colorectal adenocarcinoma cancer cell lines (HT-29). Compounds 6q and 6r efficiently inhibited both cancer cell lines tested, with IC50 values of 58.57 and 55.90 µM against OVCAR-3 and 31.36 and 42.3 µM against HT-29, respectively. The evaluation results were further supported by caspase-mediated apoptosis and docking studies, which indicated that Tyr1159 and the N-atom of the pyrrolidine moiety formed an additional hydrogen bond that stabilised the c-Met-kinase-6q complex. Overall, the results of our study suggested that Mannich-inspired indolo [2,3-b]quinoxaline adduct might make interesting lead for the development of cancer chemotherapeutics.
AB - The present work intends to synthesize a new class of small molecules featuring the quinoxaline scaffold. The indolo [2,3-b]quinoxaline-Mannich adducts were designed, synthesized and their anticancer activities were tested using MTS assay against human ovarian cancer (OVCAR-3) and female colorectal adenocarcinoma cancer cell lines (HT-29). Compounds 6q and 6r efficiently inhibited both cancer cell lines tested, with IC50 values of 58.57 and 55.90 µM against OVCAR-3 and 31.36 and 42.3 µM against HT-29, respectively. The evaluation results were further supported by caspase-mediated apoptosis and docking studies, which indicated that Tyr1159 and the N-atom of the pyrrolidine moiety formed an additional hydrogen bond that stabilised the c-Met-kinase-6q complex. Overall, the results of our study suggested that Mannich-inspired indolo [2,3-b]quinoxaline adduct might make interesting lead for the development of cancer chemotherapeutics.
UR - http://www.scopus.com/inward/record.url?scp=85145560590&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85145560590&partnerID=8YFLogxK
U2 - 10.1016/j.molstruc.2022.134627
DO - 10.1016/j.molstruc.2022.134627
M3 - Article
AN - SCOPUS:85145560590
SN - 0022-2860
VL - 1275
JO - Journal of Molecular Structure
JF - Journal of Molecular Structure
M1 - 134627
ER -