Hybrid molecules: The privileged scaffolds for various pharmaceuticals

• Published in: European journal of medicinal chemistry Vol. 124; pp. 500 - 536
• Main Authors: Shaveta, Mishra, Sahil, Singh, Palwinder
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 29-11-2016
• Subjects: Anti-Bacterial Agents - chemistry; Anti-fungal; anti-inflammatory; Anti-Inflammatory Agents - chemistry; Anti-malarial; Anti-tubercular; Antimalarials - chemistry; Drug Design; Humans; Hybrid molecules; Molecular Structure; Peptides - chemistry; Polypharmacology; NO; Anti-malarial; SAR; BPU; μM; Anti-tubercular; OA; SI; Fqa; IC50; anti-inflammatory; EC50; GI50; MIC50; TOPO; ACTs; nM; WHO; mm; CC50; MIC; BCG; μg; COX; CQ; TB; Hybrid molecules; DHFR; LOX; Anti-fungal; ROS; GSTπ; MTB
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2016.08.039

The practice of polypharmacology is not a new concept but the approaches which are being adopted for administering the two or more drugs together are varied from time to time. Taking two or more drugs simultaneously, co-formulation of two or more active agents in a single tablet and development of hybrid molecular entities capable to modulate multiple targets are the three popular approaches for multidrug therapy. The simultaneous use of more than one drug for the chemotherapy of a single disease demands a lot of patient compliance. Hence the present form of polypharmacology is gaining popularity in the form of hybrid molecules (multiple ligand approach). From the last 1-2 decades, the synthesis of hybrid molecules by the combination of different biologically relevant moieties has been under constant escalation along with their evaluation as diverse range of pharmacological agents and as potent drugs. This review is focused on the biological potential of hybrid molecules with particular mention of those exhibiting anti-fungal, anti-tuberculosis, anti-malarial, anti-inflammatory and anti-cancer activities. A comparison of the drug potency of the hybrid molecules with their individual counterparts is discussed for quantifying the significance of the concept of molecular hybridisation.
The drugs obtained by the combination of structural features of different molecules are proving to be more efficacious and safe in comparison to their individual counterparts. [Display omitted]
•Hybrid molecules exhibiting anti-fungal activity.•Hybrids showcasing anti-tubercular activity.•Hybrids profiling anti-malarial activity.•Hybrids showing anti-inflammatory properties.•Anti-cancer activity of hybrid molecules.