Draft:Hybrid molecule

A hybrid molecule is a compound obtained by combination of two (or more) pharmacophores by covalent bond that is either designed to interact with multiple targets, improve the biological properties or enhance the efficacy of the compound. The synthesis of hybrid molecules is an essential approach in the seeking of novel biologically active compounds for therapeutics. This approach has found extensive applications in pharmacological field to overcome obstacles in pharmacokinetic, toxicity, side effects on current conventional drugs, and reduce the risk of developing resistance in cancer cells.

Chemical Structures
The hybrid molecules could be a combination of two natural products or natural product pharmacophore incorporated with synthetized group molecules. In general, the structures of hybrid molecule is consist of two (or more) compounds or drugs that connected covalently by either functional group, or linker which could classified as followed:
 * 1) Directly linked hybrid compound: each molecule is connected via a functional group.
 * 2) Merged or overlapped hybrid compound: these hybrid compound has a significant difference of the structure compared to the parental compounds which as consequences form overlapping structural motifs of two molecules/drugs.
 * 3) Linker associated hybrid compound: the hybrid molecules are connected by linker to attached two constituents that have possibility to have cleavable and non-cleavable properties. The cleavable linker will be biotransformed as soon as the hybrid gets into the active site while a non-cleavable linker maintains its structure aims to retain the biological activity.

Pharmacological properties
The biological properties of hybrid molecules particularly described exhibiting anti-cancer, anti-microbial, and anti-malarial activities. The podophyllotoxin-artesunate hybrid showed a significant inhibition against HepG2 (liver cancer cell), A549 (lung cancer cell), HeLa (cervix cancer cell), and K562 (leukemia cell) and the activities is comparable to that etoposide which it already used as cancer chemotherapy. Neomycin B-ciprofloxacin hybrids with an aromatic triazole linker and aliphatic triazole linker exhibited more potent activity than (free) neomycin B which has a potential as antibacterial agent. Another example of hybrids of cinnamic acid and chalcones showed promising antimalarial activity against Plasmodium falciparum were found to be more potent than standard drug chloroquine.

Challenges
Despite the advantages and the escalating impact of hybrid molecules in medicinal area, this strategy also has potential limitations. The major problem of hybrid molecules is the large of its molecular weight (i.e. >500 Da) especially if the compound connected by a linker which possibility has a poor bioavailability and lower solubility. Another challenge in research of hybrid molecules is the favored covalent bonding between two molecules is apart from the pharmacophores region in order to maintain it bioactivity. While modification any groups in pharmacophoric area could adversely affect the biological properties also possibility to have unexpected new binding target.