An overview of molecular hybrids in drug discovery

Abstract

Current advances show that molecular hybrids of biologically active molecules can lead to powerful therapeutics. Natural products play a key role in this field. It is also believed that toxin hybrids present a great opportunity for future progress and should be further explored. Furthermore, the synthesis of hybrid organometallics should be systematically studied as it can lead to potent drugs. The crucial requirement for growth still remains the efficacy of synthesis. Hence, the development of efficient synthetic methods allowing rapid access to diverse series of hybrids must be further investigated by researchers.

Synthetic Approaches toward Vitamin B12 Conjugates

“…Delivery of an active compound (cargo) to a targeted biological site is often a very challenging task and combining a natural compound possessing the ability to pass through the cell membrane with a therapeutic agent in a hybrid/conjugate seems to be a promising approach . In this context, vitamin B 12 (B 12 , cobalamin, Cbl, 1 , Figure ), which is an essential nutrient to all mammals and certain bacteria, has been studied as a natural vector ,…”

Isatin-benzoazine molecular hybrids as potential antiproliferative agents: synthesis and in vitro pharmacological profiling

“…3-(2-(5-Fluoro-2-oxoindolin-3-ylidene)hydrazinyl)-1-methylquinoxalin-2(1 H )-one ( 9b ) – red powder (yield 75%), m.p. >300°C; IR (KBr, ν cm −1 ): 3,412 (NH) and 1,701 (C=O); 1 H NMR (DMSO- d 6 ) δ ppm: 3.71 (s, 3H, CH 3 ), 6.94–6.97 (m, 1H, Ar-H), 7.18 (t, 1H, Ar-H, J =7.0 Hz), 7.37 (t, 1H, Ar-H, J =7.5 Hz), 7.43–7.50 (m, 2H, Ar-H), 7.55 (d, 1H, Ar-H, J =8.0 Hz), 7.71 (d, 1H, Ar-H, J =7.5 Hz), 11.26 (s, 1H, NH), 13.70 (s, 1H, NH); 13 C NMR (DMSO- d 6 ) δ ppm: 29.7 (CH 3 ), 111.4 ( 3 J F-C =9.0 Hz), 115.2 ( 2 J F-C =28.8 Hz), 118.5 ( 2 J F-C =28.00 Hz), 119.0 ( 3 J F-C =9.0 Hz), 121.9, 123.9, 125.7, 128.2, 131.5, 138.3, 140.4, 147.1, 150.8, 156.8 ( 1 J F-C =239.5 Hz), 163.5, 165.9; MS (ESI) m/z : 338.0 [M+H] + ; Anal. calcd.…”

“…In the current medical era, molecular hybridization approach has stood out as a valuable and important structural modification tool useful for the discovery and development of better therapies for diverse human diseases, mostly for cancer. 1 The growing endeavors to discover hybrid drugs resulting from the combination of two or more haptophoric moieties of different bioactive substances have brought a new hope for the treatment of multifactorial disorders in recent years. Moreover, hybrid drugs can potentially overcome most of the pharmacokinetic drawbacks encountered by conventional anticancer drugs as well as provide combination therapies in a single multifunctional therapeutic agent at the target molecule conferring a more powerful, selective and safer drug compared to conventional classic treatments.…”

Multistep Synthesis and In Vitro Anticancer Evaluation of 2-Pyrazolyl-Estradiol Derivatives, Pyrazolocoumarin-Estradiol Hybrids and Analogous Compounds

“…During chemical modifications, steroids are often combined with other drugs or relevant pharmacophores via covalent bonds either acting as an effective agent or inactive carrier, or through domain integration of key structural units [ 3 , 4 ]. These multifunctional hybrid drugs or “chimeras”, which primarily serve to combat drug resistance, reduce unwanted side effects and enrich the arsenal of existing medications, offer novel therapeutic options for many diseases, including cancer, and are usually more active and specific than conventional treatments [ 5 ]. Nevertheless, steroids are privileged structures for molecular hybridization approaches due to their optically pure chiral character, conformational diversity with a varying possibility of functionalization, a hydrophobic nature that facilitates cell membrane penetration, and a wide spectrum of bioactivity [ 6 ].…”