343308-47-4Relevant academic research and scientific papers
Targeting heme Oxygenase-1 with hybrid compounds to overcome Imatinib resistance in chronic myeloid leukemia cell lines
Sorrenti, Valeria,Pittalà, Valeria,Romeo, Giuseppe,Amata, Emanuele,Dichiara, Maria,Marrazzo, Agostino,Turnaturi, Rita,Prezzavento, Orazio,Barbagallo, Ignazio,Vanella, Luca,Rescifina, Antonio,Floresta, Giuseppe,Tibullo, Daniele,Di Raimondo, Francesco,Intagliata, Sebastiano,Salerno, Loredana
supporting information, p. 937 - 950 (2018/09/29)
Heme oxygenase-1 (HO-1) is a cytoprotective enzyme and a survival-enhancing factor in a number of cancers. Chronic myeloid leukemia (CML) is a blood cancer caused by pathological kinase activity of the BCR-ABL protein, currently treated with tyrosine kinase inhibitors (TKIs) such as Imatinib (IM). However, resistance to TKIs persists in a number of patients and HO-1 overexpression has been linked with the induction of chemoresistance in CML. With this in mind, in this study, we designed and synthesized the first series of hybrid compounds obtained by combining the structures of IM, as BCR-ABL inhibitor, with imidazole-based HO-1 inhibitors. We found that many hybrids were able to inhibit the enzymatic activity of both targets and to reduce the viability of CML-IM resistant cells, showing that a single molecular entity may reduce the resistance phenomenon.
Design and synthesis of systemically active metabotropic glutamate subtype-2 and -3 (mGlu2/3) receptor positive allosteric modulators (PAMs): Pharmacological characterization and assessment in a rat model of cocaine dependence
Dhanya, Raveendra-Panickar,Sheffler, Douglas J.,Dahl, Russell,Davis, Melinda,Lee, Pooi San,Yang, Li,Nickols, Hilary Highfield,Cho, Hyekyung P.,Smith, Layton H.,D'Souza, Manoranjan S.,Conn, P. Jeffrey,Der-Avakian, Andre,Markou, Athina,Cosford, Nicholas D.P.
, p. 4154 - 4172 (2014/06/09)
As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure-activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu2 receptor PAMs and no activity at mGlu3. Compound optimization led to the identification of potent mGlu2/3 selective PAMs with no in vitro activity at mGlu1,4-8 or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu2 and PAM activity at mGlu 3. The most potent mGlu2/3 PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu2/3 PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu2/3 receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology.
Synthesis, DNA binding ability and anticancer activity of 2-heteroaryl substituted benzimidazoles linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates
Kamal, Ahmed,Pogula, Praveen Kumar,Khan, Mohammed Naseer Ahmed,Seshadri, Bobburi Naga,Sreekanth, Kokkonda
, p. 651 - 659 (2013/09/23)
As a continuation of our efforts to develop the benzimidazole-PBD conjugates as potential anticancer agents, a series of heteroaryl substituted benzimidazole linked PBD conjugates has been synthesized and evaluated for their anticancer potential in 60 human cancer cell lines. Most of the compounds exhibited promising anticancer activity and interestingly, compounds 4c and 4d displayed significant activity in most of the cell lines tested. Whereas, compound 4e showed selectivity in renal cancer cells with GI50 values of 10 and 70 nM against RXF 393 and UO-31 cell lines, respectively. Further, these compounds also showed significant DNA-binding affinity by thermal denaturation study using duplex form of calf thymus (CT) DNA.
DNA binding potential and cytotoxicity of newly designed pyrrolobenzodiazepine dimers linked through a piperazine side-armed-alkane spacer
Kamal, Ahmed,Murali Mohan Reddy,Rajasekhar Reddy,Laxman
, p. 385 - 394 (2007/10/03)
New pyrrolobenzodiazepine (PBD) dimers have been developed that are composed of two DC-81 subunits tethered to their C8 positions through piperazine moiety side-armed with alkaneoxy linkers (composed of 2-5 carbons). DNA thermal denaturation studies show
Design, synthesis, and evaluation of new noncross-linking pyrrolobenzodiazepine dimers with efficient DNA binding ability and potent antitumor activity
Kamal, Ahmed,Ramesh,Laxman,Ramulu,Srinivas,Neelima,Kondapi, Anand K.,Sreenu,Nagarajaram
, p. 4679 - 4688 (2007/10/03)
New sequence selective mixed imine-amide pyrrolobenzodiazepine (PBD) dimers have been developed that are comprised of DC-81 and dilactam of DC-81 subunits tethered to their C8 positions through alkanedioxy linkers (comprised of three to five and eight car
