Title:Highly Efficient and One-pot New Betti Bases: PEG-400 and Al2O3 Mediated Synthesis, Optimizations, and Cytotoxic Studies
Volume: 21
Issue: 15
Author(s): Reshmabanu Piludiya and Khushal M. Kapadiya*
Affiliation:
- Bioresearch and Characterization Centre, School of Science, Department of Chemistry, RK University, Rajkot, 360
020, Gujarat, India
- School of Chemistry, Cardiff University, Cardiff CF10 3AT, United Kingdom
Keywords:
Betti reaction, PEG-400, alumina catalyzed process, anti-cancer screening, single dose cell-lines study, melanoma.
Abstract:
Background: Multicomponent reactions (MCRs) have proven as one of the best alternatives
to minimize several environmental consequences, mainly the use of hazardous chemicals, byproducts,
and severe production processes. Literature reveals that MCRs with PEG-400 and metal
oxide-based greener media provide a new and useful strategy for the construction of biologically
potent organic systems.
Objective: The present study aimed to synthesize newer Betti bases by a modified Betti reaction
employing a highly efficient catalyst for the direct synthesis of a novel class of non-racemic amino
benzyl naphthol ligands under green solvent media. The involvement of the articulated framework
(4a-4j) was studied against nine cancer panels (NCI-60 cell lines) in terms of inhibiting/killing
cancer cells.
Methods: For the modification of the Betti reaction, we used 2-aminopyridin-3-ol, aromatic aldehydes,
and a naphthol system using greener media employing PEG-400 and alumina as a prime
active and highly selective catalyst. Furthermore, the antiproliferative activity against NCI-60 human
cancer cell lines (GI50) was used for the development of pharmacologically active compounds
and exhibited the single dose (10-5 M) study.
Results: Based on greener media synthesis, recompenses of ease of workup, less reaction time,
higher yield, and higher atom economy, as well as environmentally friendly, were reported. Betti
bases were obtained at a yield of 87-98% and characterized by spectroscopic techniques. Among
the synthesized scaffolds, compound 4b was found to be extra potent in melanoma cancer [MDAMB-
435], while compound 4h showed promising inhibition in leukemic cancer cell lines [HL-
60(TB) and MOLT-4].
Conclusion: A straightforward way for an efficient synthesis of Betti bases was developed via the
reaction of naphthol and aldehydes with amines in PEG-400 media. An Al2O3 was effectively catalyzed
in the Betti reaction in excellent yields without the formation of any other by-product in atom
economy and environmentally benign way. The newly synthesized hybrids were tested in vitro
against a panel of cancer cell lines, and some of the compounds exhibited significant inhibitory
anti-proliferative effects. The most potent compounds (4b and 4h) showed interesting results, and
compound 4b was found extra potent in melanoma cancer cell lines with -62% GI values.
