Phenolic 1,4-Dihydropyridines: Hantzsch Synthesis, Molecular Docking, and Antioxidant Potential: A Review

1,4-Dihydropyridines (DHPs), classically accessed through the century-old Hantzsch multicomponent reaction, remain one of the most clinically productive pharmacophores in cardiovascular medicine, underlying L-type calcium-channel blockers such as nifedipine, amlodipine, felodipine and nimodipine. Because oxidative stress is mechanistically intertwined with hypertension, endothelial dysfunction and atherosclerosis, a growing body of work has explored hybridising the DHP core with naturally occurring phenolic units (vanillin, syringaldehyde, protocatechualdehyde and related lignin-derived aldehydes) to generate dual-acting molecules capable of simultaneous calcium-channel modulation and free-radical scavenging. This review consolidates the classical and contemporary (2012–2026) literature on Hantzsch DHP synthesis — including green, catalytic and microwave-assisted variants — on the structural biology of the CaV1.2 dihydropyridine receptor site as resolved by cryo-electron microscopy, on structure-based molecular docking as a rational pre-synthetic screening tool, and on the physicochemical basis of phenolic antioxidant activity (hydrogen-atom transfer, single-electron transfer–proton transfer and sequential proton-loss electron-transfer mechanisms). Reported phenolic-DHP and related heterocyclic hybrids combining antioxidant, anticancer, antidiabetic and antimicrobial activity are critically compared, and the structure–activity principles that should guide the rational design of new dual-acting calcium-channel-modulating antioxidant candidates are synthesised. The review concludes by identifying gaps — particularly the scarcity of studies pairing structure-based CaV1.2 docking with standardised tri-assay (DPPH/ABTS/FRAP) antioxidant profiling of a single matched phenolic-DHP series — and outlines a feasible experimental and computational workflow for future investigation.