Navriti Chadha

Oxindole: A chemical prism carrying plethora of therapeutic benefits.

Oxindole has emerged as a valuable scaffold in medicinal chemistry possessing diverse range of pharmacological activities. Its value has further been increased by its natural occurrence as alkaloids in variety of plants. It was first extracted from the cat claws plant Uncaria tomentosa found in the Amazon rainforest and other tropical areas of South and Central America. Traditionally as well as present emerging therapeutic potential of oxindole nucleus has captured the interest of medicinal chemists to synthesize novel oxindole derivatives. In the present review the authors have integrated its chemistry and synthetic strategies developed after 1945. Also the information of naturally occurring oxindole alkaloids has been incorporated. The detailed pharmacological activities including anti-cancer, anti-HIV, antidiabetic, antibacterial, antioxidant, kinase inhibitory, AChE inhibitory, anti-leishmanial, β3 adrenergic receptor agonistic, phosphatase inhibitory, analgesic, spermicidal, vasopressin antagonists, progesterone antagonists, neuroprotection, and NMDA blocker activities of oxindole derivatives alongwith their SAR has also been discussed in detail. Additionally, information regarding the oxindole derivatives in clinical trials has been incorporated. Thus, this review will provide insights for the synthetic as well as medicinal chemist for the designing and synthesis of novel oxindole derivatives with novel improved range of pharmacological implications.

Indoles as therapeutics of interest in medicinal chemistry: Bird's eye view

Indoles constitute extensively explored heterocyclic ring systems with wide range of applications in pathophysiological conditions that is, cancer, microbial and viral infections, inflammation, depression, migraine, emesis, hypertension, etc. Presence of indole nucleus in amino acid tryptophan makes it prominent in phytoconstituents such as perfumes, neurotransmitters, auxins (plant hormones), indole alkaloids etc. The interesting molecular architecture of indole makes them suitable candidates for the drug development. This review article provides an overview of the chemistry, biology, and toxicology of indoles focusing on their application as drugs. Our effort is to corroborate the information available on the natural indole alkaloids, indole based FDA approved drugs and clinical trial candidates having diverse therapeutic implementations. This compiled information may serve as a benchmark for the alteration of existing ligands to design novel potent molecules with lesser side effects.

Hybrids: a new paradigm to treat Alzheimer's disease

Alzheimer‘s disease (AD) is a complex neurodegenerative condition with several target proteins contributing to its etiology. With 35.6 million cases worldwide documented in 2011, AD constitutes a devastating health, political, economic, and social problem for all nations. The cases are expected to increase beyond 107 million in 2050; unless an advanced therapy having a capability to delay the disease progression is developed. The curative paradigm of one-compound one-target that has been followed so far has not reached the desired mark. The research focus moved towards single molecule targeting two or more pathogenic mechanisms involved in neuronal death. Over the last few years, medicinal chemists have been paying attention to the design and synthesis of the hybrid molecules that are comprised of two pharmacophores from well-established chemical scaffolds endowed with requisite biological activities in a single entity. The hybrid-based approach has grown to be a central point in the medicinal chemistry field. Various important pharmacophores used for AD have been combined with selected biologically active molecules to get homo- and heterodimers with improved efficacy with additional supplementary actions. This review summarizes the pathogenesis of AD and various progress in the design of hybrid molecules based on the one-compound-various targets paradigm for AD therapy.

Dual inhibitors of Janus kinase 2 and 3 (JAK2/3): designing by pharmacophore- and docking-based virtual screening approach

JAK2 and JAK3 are non-receptor protein tyrosine kinases implicated in B-cell- and T-cell-mediated diseases. Both enzymes work via different pathways but are involved in the pathogenesis of common lymphoid-derived diseases. Hence, targeting both Janus kinases together can be a potential strategy for the treatment of these diseases. In the present study, two separate pharmacophore-based 3D-QSAR models ADRR.92 (

Active site fingerprinting and pharmacophore screening strategies for the identification of dual inhibitors of protein kinase C \((\hbox {PKC}{\upbeta })\) and poly (ADP-ribose) polymerase-1 (PARP-1)

Q_{\mathrm{test}}^{2} 0.663, R^{2}_{\mathrm{train}} 0.849

Pharmacophore based design of some multi-targeted compounds targeted against pathways of diabetic complications

Qtest20.663,Rtrain20.849, F value 219.3) for JAK2 and ADDRR.142 (

Thiazolidine-2,4-Dione: A Potential Weapon for Targeting Multiple Pathological Conditions

Q^{2}_{\mathrm{test}}0.655, R_{\mathrm{train}}^{2}