Research Projects

Gamma-aminobutyric acid type A (GABAA) receptors are the main inhibitory neurotransmitter receptors in the central nervous system (CNS). They are heteropentamers with different subunits, forming a central pore permeable to chloride and bicarbonate ions. The most abundant GABAA receptor subtype in the mammalian CNS is an assembly of two α1, two β2, and one γ2 subunits. GABAA receptors are targets for various drugs used to treat anxiety, panic, insomnia, and epilepsy. However, current drugs like benzodiazepines are associated with side-effects due to a lack of receptor-subtype selectivity. The scaffold diversity of synthetic drugs and experimental compounds targeting GABAA receptors is limited, making it crucial to discover allosteric GABAA receptor modulators with novel scaffolds that may target binding sites other than the benzodiazepine binding site. In recent years, various natural products with scaffolds new for GABAA receptors have been reported, and compounds such as valerenic acid and magnolol have been shown to interact at a benzodiazepine independent allosteric binding site. However, there is a lack of medicinal chemistry efforts to develop novel GABAA receptor modulators starting from valerenic acid or related molecules isolated from the Valeriana sp. A collaboration research institute with a large farm resource has been working on drug discovery programs from medicinal plants, including Valeriana officinalis, to identify architecturally fascinating and biologically potent molecules. The proposal focuses on the isolation and structural reformation of CNS-active molecules from plant origin and their in-house bio-evaluation.