Design and synthesis of novel conformationally constrained 7,12-dihydrodibenzo[b,h][1,6] naphthyridine and 7H-Chromeno[3,2-c] quinoline derivatives as topoisomerase I inhibitors: In vitro screening, molecular docking and ADME predictions.

Novel non-camptothecin (non-CPT) class of conformationally constrained, hitherto unknown 7,12-dihydrodibenzo[b,h][1,6] naphthyridine and 7H-Chromeno[3,2-c] quinoline derivatives have been designed, synthesized and evaluated for anti-cancer activity. In vitro anti-proliferation evaluation against human cancer cell lines (A549 and MCF-7) exhibited significant cytotoxicity. Among the derivatives (8-24), 8 (IC50 0.44 µM and IC50 0.62 µM) and 12 (IC50 0.69 µM and IC50 0.54 µM) were identified as the most promising candidate against A-549 and MCF-7 cancer cell lines respectively. Topo I inhibitory activity of 8 and 12 suggested that, they may be developed as potential anti-cancer molecules in future and rationalized by docking analysis with effective binding modes. Further, in silico ADME prediction studies of all derivatives were found promising, signifying the drug like properties. In precise, the present investigation displays a new strategy to synthesize and emphasis on anticancer activities of conformationally constrained dibenzo[b,h][1,6] naphthyridine derivatives and Chromeno[3,2-c] quinoline derivatives in the context of cancer drug development and refinement.

Amine-Functionalized Graphene Oxide-Stabilized Pd Nanoparticles (Pd@APGO): A Novel and Efficient Catalyst for the Suzuki and Carbonylative Suzuki-Miyaura Coupling Reactions.

Palladium nanoparticles (NPs) are decorated on the surface of an amine-functionalized graphene oxide (Pd@APGO) and characterized by using various analytical techniques. In this methodology, the surface of graphene oxide is modified using the amine functional groups which help stabilization and distribution of Pd NPs very well and increases the surface electron density of NPs by electron donating from amine groups. This developed catalyst shows a high catalytic activity toward the Suzuki coupling and carbonylative Suzuki-Miyaura coupling reactions at mild reaction conditions. The amine on the graphene oxide plays a very crucial role to stabilize and increase the electron density of Pd NPs and prevents the leaching of Pd metals. The Pd@APGO catalyst showed excellent catalytic activity (>90%) with a large range of substrates for both of the reactions and provides five recycle runs without the loss of its activity.

Palladium-Catalyzed Oxidative N-Dealkylation/Carbonylation of Tertiary Amines with Alkynes to α,ß-Alkynylamides.

The first highly effective Pd/C-catalyzed oxidative N-dealkylation/carbonylation of various aliphatic as well as cyclic tertiary amines with alkynes has been described. The selective sp(3) C-N bond activation of tertiary amines at the less steric side using O2 as a sole oxidant and a plausible reaction pathway for the reaction are discussed. The general and operationally simple methodology provides an alternative for the synthesis of a wide range of alk-2-ynamide derivatives under mild conditions. The present protocol is ecofriendly and practical, and it shows significant recyclability.

Pd/C-Catalyzed Aminocarbonylation of Aryl Iodides via Oxidative C-N Bond Activation of Tertiary Amines to Tertiary Amides.

This work reports oxidative N-dealkylation/carbonylation of tertiary amines to tertiary amides by using molecular oxygen as a sole oxidant using a Pd/C catalyst. This protocol is free from ligands, additives, bases, and cocatalysts. Different tertiary amines as well as aryl iodides have been examined for this transformation, providing desired products in good to excellent yield.

Synthesis of anomeric 1,5-anhydrosugars as conformationally locked selective α-mannosidase inhibitors.

Anomeric 1,5-anhydrosugar 2 was synthesized from d-glucose derived N-Cbz protected aminodiol 8. The key step involves, acid catalyzed hydrolysis of 1,2-acetonide group in 8 to get hemiacetal that concomitantly undergoes formation of the pyranose ring by attack of C-3 hydroxyethyl group on anomeric C-1, leading to the formation of dioxabicyclo[3.2.1]octane skeleton which on hydrogenolyis gave 2. The glycosidase inhibitory activities of hydroxy- and amino-substituted anomeric 1,5-anhydrosugars 1 and 2, respectively, showed selective inhibition of α-mannosidase. These results were substantiated by molecular docking studies using WHAT IF software and AUTODOCK 4.0 program.

Synthesis of an adenine nucleoside containing the (8'R) epimeric carbohydrate core of amipurimycin and its biological study.

The (8'R) epimeric carbohydrate core 2 of amipurimycin was synthesized from D-glucose derived allylic alcohol 3 in 11 steps and 13% overall yield. The key steps involve an acid-catalyzed acetonide ring opening of 9 with concomitant formation of an unprecedented pyranose ring skeleton to give 2,7-dioxabicyclo[3.2.1]octane 10. The α-orientation of the furan ring in 10 readily allows the stereoselective ß-glycosylation and opening of the furanose ring that on removal of protecting groups affords the pyranosyl adenine nucleoside 2. The antifungal and anticancer activities of 2 were studied.

Synthesis of gamma-hydroxyalkyl substituted piperidine iminosugars from D-glucose.

D-Glucose was converted to synthetic equivalent of meso-pentodialdose, namely 3-C-(1'-aminoethyl)-alpha-d-ribo-pentodialdo-1,4-furanose 10 that gives an easy access to manipulate the aldehyde functionalities on either sides to get enantiomeric pair of 3. Thus, reduction of C5-aldehyde followed by hydrolysis of 1,2-acetonide functionality and reductive aminocyclization with C1-aldehyde afforded gamma-1,2-dihydroxyethyl piperidine iminosugar 3. On the other hand, first reductive aminocyclization with C5-aldehyde gave piperidine ring skeleton 12 that on removal of 1,2-acetonide and reduction of C1-aldehyde gave ent-3 while chopping of C1-aldehyde in 12 and reduction afforded gamma-hydroxymethyl piperidine iminosugar 4.