274677-71-3Relevant academic research and scientific papers
Discovery of novel phosphatidylcholine-specific phospholipase C drug-like inhibitors as potential anticancer agents
Barker, David,Brar, Harpreet Kaur,Eurtivong, Chatchakorn,Leung, Euphemia,Leung, Ivanhoe K. H.,Paulin, Emily K.,Pilkington, Lisa I.,Rees, Shaun,Reynisson, Jóhannes,Sharma, Nabangshu,White, Reuben M.,Xu, Chris Sun,van Rensburg, Michelle
supporting information, (2019/12/24)
Phosphatidylcholine–specific phospholipase C (PC-PLC) is a promising target for new anticancer treatment. Herein, we report our work in the discovery of novel drug-like PC-PLC inhibitors. Virtual screening led to the identification of promising hits from
DNA-binding affinity and anticancer activity of β-carboline-chalcone conjugates as potential DNA intercalators: Molecular modelling and synthesis
Shankaraiah, Nagula,Siraj,Nekkanti, Shalini,Srinivasulu, Vunnam,Sharma, Pankaj,Senwar, Kishna Ram,Sathish, Manda,Vishnuvardhan,Ramakrishna, Sistla,Jadala, Chetna,Nagesh, Narayana,Kamal, Ahmed
, p. 130 - 139 (2015/03/30)
A new series of DNA-interactive β-carboline-chalcone conjugates have been synthesized and evaluated for their in vitro cytotoxicity and DNA-binding affinity. It has been observed that most of these new hybrids have shown potent cytotoxic activities on A-549 (lung adenocarcinoma) cell lines with IC50 values lower than 10 μM. The hybrid 7b is more effective against some of the selected cancer cell lines with IC50 values less than 50 μM. In addition, compounds 7e, 7k, 7p-u has displayed significant elevation in ΔTm of DNA in comparison to Adriamycin, suggesting significant interaction and remarkable DNA stabilization. The DNA intercalation of these new hybrids has been investigated by fluorescence titration, DNA viscosity measurements, molecular docking as well as molecular dynamics and the results are in agreement with the thermal denaturation studies.
Design and synthesis of C3-pyrazole/chalcone-linked beta-carboline hybrids: Antitopoisomerase I, DNA-interactive, and apoptosis-inducing anticancer agents
Kamal, Ahmed,Srinivasulu, Vunnam,Nayak, V. Lakshma,Sathish, Manda,Shankaraiah, Nagula,Bagul, Chandrakant,Reddy, N. V. Subba,Rangaraj, Nandini,Nagesh, Narayana
, p. 2084 - 2098 (2014/11/07)
A series of β-carboline hybrids bearing a substituted phenyl and a chalcone/(N-acetyl)-pyrazole moiety at the C1 and C3 positions, respectively, was designed, synthesized, and evaluated for anticancer activity. These new hybrid molecules showed significant cytotoxic activity, with IC50 values ranging from 2.0 μM to 80 μM, and the structure-activity relationships (SAR) associated with substitutions at positions 1 and 3 of these hybrids was clearly addressed. Further, induction of apoptosis was confirmed by Annexin V-FITC, Hoechst staining, and DNA fragmentation analysis. In addition, DNA photocleavage studies proved that two of the hybrids, (E)-1-(furan-2-yl)-3- (1-(4-(trifluoromethyl)phenyl)-9H-pyrido[3,4-b]indol-3-yl)prop-2-en-1-one (7 d) and 1-(3-(furan-2-yl)-5-(1-(4-(trifluoromethyl)phenyl)-9H-pyrido[3,4-b]indol-3- yl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (8 d) could effectively cleave pBR322 plasmid DNA upon irradiation with UV light. Active hybrid 8 d inhibited DNA topoisomerase I activity efficiently and preserved DNA in the supercoiled form. To further corroborate the biological activities, as well as to understand the nature of the interaction of these hybrids with DNA, spectroscopic studies were also performed. Unlike simple β-carboline alkaloids, the binding mode of these new hybrid molecules with DNA was not similar, and both biophysical as well as molecular docking studies speculated a combilexin-type of interaction with DNA. Further, an in silico study of these β-carboline hybrids revealed their drug-like properties.
Synthesis and cytotoxicity evaluation of (tetrahydro-β-carboline)-1,3,5-triazine hybrids as anticancer agents
Kumar, Ravi,Gupta, Leena,Pal, Pooja,Khan, Shahnawaz,Singh, Neetu,Katiyar, Sanjay Babu,Meena, Sanjeev,Sarkar, Jayanta,Sinha, Sudhir,Kanaujiya, Jitendra Kumar,Lochab, Savita,Trivedi, Arun Kumar,Chauhan, Prem M.S.
experimental part, p. 2265 - 2276 (2010/06/17)
A series of tetrahydro-β-carbolines and 1,3,5-triazine hybrids have been synthesized and evaluated for their cytotoxicity against a panel of eight human cancer cell lines and normal human fibroblasts (NIH3T3). It led us to discovery of racemic compounds 69, 71 and 75, which are selectively cytotoxic towards KB (oral cancer) cell line with IC50 values of 105.8, 664.7 and 122.2?nM, respectively; while their enantiopure forms are less active and not selective. Enantiopure compound 42 showed 2.5 times more selectivity towards MCF7 cells over normal fibroblast NIH3T3 cells with an IC50 value of 740?nM, also arrests cell cycle in G1 phase and induces apoptosis in MCF7 and MDA MB231cell lines.
Synthesis of diketopiperazine-based carboline homodimers and in vitro growth inhibition of human carcinomas
Deveau, Amy M.,Costa, Nancy E.,Joshi, Elizabeth M.,Macdonald, Timothy L.
scheme or table, p. 3522 - 3525 (2009/04/06)
Starting from d- or l-tryptophan, we have synthesized and characterized six compounds 2.29-2.31a and b that belong to a class of nitrogen heterocycles: the carboline-based homodimers. Each individual homodimer features a 1,3-trans relationship on each side of the central diketopiperazine core, but differs in absolute stereochemistry and also in substitution on the 4′ and 4″ oxygens (-Bn, -CH3, or -H). The in vitro cytotoxicity of the six compounds was evaluated by measuring the growth inhibition in NCI-H520 and PC-3 human carcinoma cells. Phenol 2.30a inhibited cancer cell growth approximately three times better than its enantiomer 2.30b and possessed a GI50 comparable to the clinically used agent etoposide in both cell lines. We have concluded that both the stereochemistry imparted by l-tryptophan and the presence of hydroxy substituents at the 4′ and 4″ positions are necessary to generate cytotoxic properties in the homodimer class. We are now employing 2.30a as a new lead compound in our efforts to discover improved indole-based cancer chemotherapeutics.
Synthesis of 2-[3-(7-Chloro-quinolin-4-ylamino)-alkyl]-1-(substituted phenyl)-2,3,4,9-tetrahydro-1H-β-carbolines as a new class of antimalarial agents
Gupta, Leena,Srivastava, Kumkum,Singh, Shubhra,Puri,Chauhan, Prem M.S.
scheme or table, p. 3306 - 3309 (2009/04/11)
A series of hybrid molecules 2-[3-(7-Chloro-quinolin-4-ylamino)-alkyl]-1-(substituted phenyl)-2,3,4,9-tetrahydro-1H-β-carbolines have been synthesized and screened for their in vitro antimalarial activity against chloroquine-sensitive strains of Plasmodium falciparum. Compounds 26, 32, and 34 have shown MIC in the range of 0.05-0.11 μM and are in vitro several folds more active than chloroquine.
Synthesis and evaluation of tryprostatin B and demethoxyfumitremorgin C analogues
Wang, Haishan,Usui, Takeo,Osada, Hiroyuki,Ganesan
, p. 1577 - 1585 (2007/10/03)
Tryprostatin B and demethoxyfumitremorgin C are fungal inhibitors of mammalian cell cycle progression at the G2/M transition. N-Alkyl derivatives of the L-Trp-L-Pro diketopiperazine were prepared as analogues of tryprostatin B, and two of these
