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INNOSC Theranostics and
            Pharmacological Sciences                                      Transformative natural product-drug combinations



            of antimicrobial resistance (AMR) complicates treatment   the feasibility of producing these compounds at scale.
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            efficacy by enabling pathogens to evolve mechanisms   Genetic engineering has also been utilized to produce
            that resist drug therapy, leading to persistent infections   complex natural products like artemisinin through
            and increased transmission rates. According to Cesur   yeast, addressing challenges associated with traditional
                       1
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            and Demiröz  and Olga  et  al.,  this phenomenon not   extraction methods from Artemisia annua. 11
            only endangers health outcomes but also amplifies the
            burden on healthcare systems worldwide. The World   1.2. The role of medicinal plants in combating AMR
            Health Organization  underscores the severity of the   Medicinal plants are rich sources of diverse phytochemicals,
                             3
            issue, reporting that AMR causes approximately 700,000   the composition of which varies depending on the plant
            deaths annually. Projections indicate that this figure could   species, its geographical location, and the extraction
            escalate to 10 million deaths per year by 2050 if effective   solvent used. 13-16  Studies by Khosravi,  Alzohairy,  and
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            interventions  are  not  implemented.  Several  interrelated   Jafarnejad et al.  suggest that aqueous plant extracts may
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            factors, such as overuse and misuse of antibiotics in   effectively treat bacterial infections, sometimes showing
            medicine, agriculture, and animal husbandry, drive the   comparable or even superior efficacy to certain antibiotics
            escalation of AMR. Practices such as over-prescription,   while  potentially reducing the  development  of bacterial
            self-medication, and the use of antibiotics  as growth   resistance. Drug repurposing also offers a promising
            promoters in livestock exacerbate the problem.  The   strategy in the fight against drug-resistant pathogens. This
                                                     4
            pipeline for new antibiotics is worryingly sparse due   approach involves using known compounds or existing
            to significant financial and scientific barriers faced by   drugs to treat recalcitrant infections and diseases.
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            pharmaceutical companies.  Moreover, environmental   Moreover, two potent bioactive compounds with diverse
                                   5
            pollution and climate change contribute to the spread   pharmacological activities present new opportunities
            and mutation of resistant pathogens, further complicating   for treating resistant infections. For example, the triple
            efforts to control AMR. 4,6                        synergistic inhibitory activities of riboprine and forodesine
                                                               against the enzymes RNA-dependent RNA polymerase,
            1.1. Addressing AMR with medicinal plant           exonuclease, and adenosine kinase in the replication of
            compounds                                          severe acute respiratory syndrome coronavirus 2. 21,22
            The production of bioactive compounds from medicinal   This review explores strategies to develop, modify, or
            plants necessitates the use of sophisticated techniques to   optimize potent active compounds using a combinatorial
            ensure scalability and efficiency. Direct extraction can   synthetic method that utilizes phytoconstituents present
            be  impractical, prompting the  need  for  semi-synthesis,   in plant extracts. The aim is to enhance their efficacy and
            total synthesis, and biotechnological approaches as viable   reduce the potential for pathogen resistance to existing
            alternatives. Semi-synthesis involves modifying natural   or new compounds. Evidence from attenuated total
            compounds to enhance their efficacy or ease of production.   reflectance-Fourier transform infrared spectroscopy (ATR-
            A  notable example is the production of the critical   FTIR), gas chromatography-mass spectrometry (GC-MS),
            anticancer drug paclitaxel (Taxol). Advances in synthetic   and antibacterial studies in the literature is presented to
            chemistry have enabled the development of total synthesis   support these approaches.
            routes for compounds like paclitaxel and its derivatives,
            improving availability and reducing the costs associated   2. Development and testing of
                                          7,8
            with natural extraction methods.  Biotechnological   antimicrobial strategies incorporating
            methods, including genetic engineering and microbial   medicinal plant
            fermentation,  have  revolutionized  the  production  of
            complex natural products. For instance, genes responsible   Before plant extracts can be utilized, a meticulous process
            for paclitaxel biosynthesis have been successfully   involving harvesting, pre-treatment, and various extraction
            integrated into microorganisms such as  Escherichia coli   methods must be followed to ensure the quality and efficacy
            and Saccharomyces cerevisiae, enabling these microbes to   of the final product. The initial step, harvesting, must be
            produce paclitaxel precursors.  In addition, plant cell culture   timed appropriately to capture the peak concentration of
                                   7
            techniques have been employed to cultivate paclitaxel   desired phytochemicals. Pre-treatment processes such as
            from Taxus cell cultures.  The semi-synthesis of bioactive   drying,  grinding,  and  sometimes  fermentation  prepare
                               8,9
            terpenoids, steroids, and polyketides from uncultivated   the plant material for extraction, thereby enhancing the
            bacterial symbionts demonstrates the potential of these   efficiency and yield of the subsequent steps. Different
            approaches. 10,11  Biotechnological advancements, including   extraction methods, such as maceration, infusion,
            plant tissue culture and microbial fermentation, highlight   decoction, and modern techniques like supercritical fluid


             Volume 8 Issue 2 (2025)                        88                               doi: 10.36922/itps.4068
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