Ferrocene-appended pharmacophores: an exciting approach for modulating the biological potential of organic scaffolds

Two exemplary contributions of organometallics in medicinal chemistry, ferroquine and ferrocifen, which exhibit excellent anti-plasmodial and anti-cancer activities, respectively, have opened a new field called medicinal organometallic chemistry. This field has been gaining significant interest due to the recent upsurge in ferrocene-linked organic frameworks with promising biological potential. The success of ferrocene is due to the sustained efforts by organic medicinal chemists and its inherent stability in air, heat and light, low toxicity, low cost and reversible redox properties. The replacement of the aryl/heteroaryl core with a ferrocene nucleus in organic molecules imparts a significant change not only in their molecular properties, such as solubility and hydro-/lipophilicity, but also improves the activities of bioactive compounds. Ferrocifen (ferrocene analogue of hydroxytamoxifen) possesses the remarkable feature of being anti-proliferative against both the MCF-7 (hormone dependent) and MDA-MB-231 (hormone independent) breast cancer cell lines. Accordingly, this review article is aimed at updating researchers on the recent developments (2014-18) on the synthesis and evaluation of ferrocene-containing bio-active pharmacophores with emphasis on their structure-activity relationship and mechanism of action. The present review article describes the recent developments (2014-18) on the synthesis of ferrocene-based pharmacophores with the specific benefits of introducing/replacing organic pharmacophores with the ferrocene core for desired bioactivities.