Praveen Reddy Adiyala

Access to Imidazo[1,2-a]pyridines via Annulation of α-Keto Vinyl Azides and 2-Aminopyridines

A novel strategy for the synthesis of imidazo[1,2-a]pyridines via efficient catalyst/metal-free annulations of α-keto vinyl azides and 2-aminopyridines is described. Several imidazo[1,2-a]pyridines were synthesized from readily available vinyl azides and 2-aminopyridines and obtained in highly pure form by simply evaporating the reaction solvent. This remarkably high yielding and atom economical protocol allows the formation of three new C-N bonds through cascade reactions and rearrangements.

One-pot, three-component approach to the synthesis of 3,4,5-trisubstituted pyrazoles.

An operationally simple and high yielding protocol for the synthesis of polyfunctional pyrazoles has been developed through one-pot, three-component coupling of aldehydes, 1,3-dicarbonyls, and diazo compounds as well as tosyl hydrazones. The reaction proceeds through a tandem Knoevenagel condensation, 1,3-dipolar cycloaddition, and transition metal-free oxidative aromatization reaction sequence utilizing molecular oxygen as a green oxidant. The scope of the reaction was studied by varying the aldehyde, 1,3-dicarbonyl, and diazo component individually.

Rapid access to novel 1,2,3-triazolo-heterocyclic scaffolds via tandem Knoevenagel condensation/azide-alkyne 1,3-dipolar cycloaddition reaction in one pot.

An operationally simple, one-pot, two-step cascade method has been developed to afford biologically important fused 1,2,3-triazolo-heterocyclic scaffolds from 2-alkynyl aryl(heteroaryl) aldehydes and phenacyl azides. This unique atom economical transformation engages four reactive centers (aldehyde, alkyne, active methylene, and azide) under metal-free catalysis.

Catalyst-free stereoselective cyclopropanation of electron deficient alkenes with ethyl diazoacetate

Doubly activated electron deficient alkenes react with ethyl diazoacetate in a Michael Initiated Ring Closure (MIRC) fashion to yield highly diastereoselective cyclopropanes even without any added base or metal catalyst. Following the strategy, a one-pot, two-step, three-component reaction of aldehydes, malononitrile/ethyl cyanoacetate, and ethyl diazoacetate was successfully developed.

Diastereoselective synthesis of spiro[cyclopropane-1,3′-indolin]-2′-ones through metal-free cyclopropanation using tosylhydrazone salts

Transition metal-free diastereoselective cyclopropanation of 3-methyleneindolin-2-ones using tosylhydrazone salts as a safe alternative to diazo-compounds was achieved in high yields. All the synthesized compounds were evaluated for their biological activity against three different human cancer cell lines DU-145 (prostate cancer), Hela (cervical cancer) and A-549 (lung cancer). Compounds 3b and 3i exhibited promising anticancer activity (IC50 < 10 μM) against the studied cell lines.

Synthesis of α-amino amidines through molecular iodine-catalyzed three-component coupling of isocyanides, aldehydes and amines

Summary A facile and efficient synthetic protocol for the synthesis of α-amino amidines has been developed using a molecular iodine-catalyzed three-component coupling reaction of isocyanides, amines, and aldehydes. The presented strategy offers the advantages of mild reaction conditions, low environmental impact, clean and simple methodology, high atom economy, wide substrate scope and high yields.

Synthesis of 2-anilinopyridine–arylpropenone conjugates as tubulin inhibitors and apoptotic inducers

A series of new (Z)-3-(arylamino)-1-(2-(arylamino)pyridin-3-yl)prop-2-en-1-one conjugates 9a–p were synthesized and evaluated for their cytotoxic activity against some human cancer cell lines. Some of the treated compounds like 9a, 9g and 9j showed significant activity with IC50 values ranging from 0.51 to 1.29 μM. Flow cytometry results revealed that for A549 cells these compounds caused accumulation of cells in the G2/M phase. Interestingly, compound 9a demonstrated a considerable inhibitory effect on tubulin polymerization and showed significant inhibition of tubulin polymerization with an IC50 value of 1.34 μM, whereas nocodazole showed antitubulin activity with an IC50 value 2.64 μM. Further, Hoechst staining and activation of caspase-3 suggested that these conjugates induced cell death by apoptosis. Fluorescence based competitive colchicine binding assay and docking studies suggest that these conjugates 9a and 9g bind to the tubulin perfectly at the colchicine binding site.

Development of pyrrolo[2,1-c][1,4]benzodiazepine β-glucoside prodrugs for selective therapy of cancer

Cancer chemotherapy has several limitations such as often insufficient differentiation between malign tissue and benign tissue. The clinical utility of the pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are inadequate because of the lack of selectivity for tumor tissues, high reactivity of the pharmacophoric imine functionality, low water solubility, and stability. To address these limitations two new β-glucoside prodrugs of PBDs have been synthesized and evaluated for their potential use in selective therapy of solid tumors by ADEPT. The preliminary studies reveal the prodrugs are much less toxic compared to the parent moieties. These prodrugs are activated by β-glucosidase to produce the active cytotoxic moiety signifying their utility in ADEPT of cancer. The prodrugs 1a and 1b were evaluated for their cytotoxic activity in three human cancer cell lines, i.e., A375, MCF-7 and HT-29 by employing MTT assay. The results reveal that the prodrugs have shown significant cytotoxic activity in the presence of enzyme. Another important property of these molecules is their enhanced water solubility and stability, which are essential for a molecule to be an effective drug.