polymers Review Solid-Phase Extraction of Active Compounds from Natural Products by Molecularly Imprinted Polymers: Synthesis and Extraction Parameters Sazlinda Kamaruzaman 1,2, * , Najihah Mohammad Nasir 1 , Siti Munirah Mohd Faudzi 1,2 , Noorfatimah Yahaya 3 , Nor Suhaila Mohamad Hanapi 4 and Wan Nazihah Wan Ibrahim 4   Citation: Kamaruzaman, S.; Nasir, N.M.; Mohd Faudzi, S.M.; Yahaya, N.; Mohamad Hanapi, N.S.; Wan Ibrahim, W.N. Solid-Phase Extraction of Active Compounds from Natural Products by Molecularly Imprinted Polymers: Synthesis and Extraction Parameters. Polymers 2021, 13, 3780. https://doi.org/10.3390/ polym13213780 Academic Editor: Tetyana Budnyak Received: 6 September 2021 Accepted: 21 October 2021 Published: 31 October 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Chemistry, Faculty of Science, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia; msnajihahnasir2496@gmail.com (N.M.N.); sitimunirah@upm.edu.my (S.M.M.F.) 2 Natural Medicines and Product Research Laboratory (NaturMeds), Institute of Bioscience (IBS), Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia 3 Integrative Medicine Cluster, Advanced Medical and Dental Institute (AMDI), Universiti Sains Malaysia, Bertam, Kepala Batas, Penang 13200, Malaysia; noorfatimah@usm.my 4 Faculty of Applied Sciences, Universiti Teknologi MARA, Shah Alam 40450, Selangor, Malaysia; norsuhaila979@salam.uitm.edu.my (N.S.M.H.); wannazihah@salam.uitm.edu.my (W.N.W.I.) * Correspondence: sazlinda@upm.edu.my Abstract: Molecularly imprinted polymers (MIPs) are synthetic polymers with a predetermined selectivity for a particular analyte or group of structurally related compounds, making them ideal materials for separation processes. Hence, in sample preparation, MIPs are chosen as an excellent material to provide selectivity. Moreover, its use in solid-phase extraction, also referred to as molecular imprinted solid phase extraction (MISPE), is well regarded. In recent years, many papers have been published addressing the utilization of MIPs or MISPE as sorbents in natural product applications, such as synthesis. This review describes the synthesis and characterization of MIPs as a tool in natural product applications. Keywords: natural products; molecular imprinted solid-phase extraction; polymerization technique 1. Introduction Natural products provide an infinite source for new therapeutic leads, for a treatment of a wide spectrum of disease. Historically, plants have formed the basis of traditional medicine system as documented in Mesopotamia (dating around ~2600 BCE), Egyptian medicine (dated from ~2900 BCE), “Ebers Papyrus” (dated from ~1500 BCE), Chinese Mate- ria Medica (firstly dated in ~1100 BCE), Indian Ayurvedic system (dated from <1000 BCE) and by the Greeks and Romans, who’s contributed to the rational development of herbal- based drugs in Western world [1]. Pharmaceutical research expanded after the World War II (WW2) due to the discovery of penicillin, and by 1990, approximately 80% of drugs were either natural products or natural-based synthetic analogs were reported [2]. Some pertinent examples of plant-derived drugs are khellin, isolated from Ammi visnaga (L.) Lamk., which led to the development of bronchodilator agent, chromolyn (in the form of sodium chromoglycate) [3]. Plant-based system have continued to play an important role in healthcare since then, with the urgent needs for the searching of new pharmaceutics to treat cancer, HIV, andinfectious diseases. Besides plants, marine organism and microorganism also significantly contributed towards the intensive investigation of nature as a source of novel bioactive agents. To name a few, halichondrin B, marine-derived anticancer agents, was derived from a complex polyether of several sponge sources [4], and bryostatin 1, which was isolated from complex macrolide extracts of the bryozoan, Bugula neritina [5,6]. Meanwhile, microorganism offers important antibacterial agents such as penicillins (from Penicillium species), and cephalosporins (from Cephalosporium acremonium)[7]. Polymers 2021, 13, 3780. https://doi.org/10.3390/polym13213780 https://www.mdpi.com/journal/polymers