Semisynthetic Compounds Research Articles

The Role of Natural and Semi-Synthetic Compounds in Ovarian Cancer: Updates on Mechanisms of Action, Current Trends and Perspectives.

Ovarian cancer represents a major health concern for the female population: there is no obvious cause, it is frequently misdiagnosed, and it is characterized by a poor prognosis. Additionally, patients are inclined to recurrences because of metastasis and poor treatment tolerance. Combining innovative therapeutic techniques with established approaches can aid in improving treatment outcomes. Because of their multi-target actions, long application history, and widespread availability, natural compounds have particular advantages in this connection. Thus, effective therapeutic alternatives with improved patient tolerance hopefully can be identified within the world of natural and nature-derived products. Moreover, natural compounds are generally perceived to have more limited adverse effects on healthy cells or tissues, suggesting their potential role as valid treatment alternatives. In general, the anticancer mechanisms of such molecules are connected to the reduction of cell proliferation and metastasis, autophagy stimulation and improved response to chemotherapeutics. This review aims at discussing the mechanistic insights and possible targets of natural compounds against ovarian cancer, from the perspective of medicinal chemists. In addition, an overview of the pharmacology of natural products studied to date for their potential application towards ovarian cancer models is presented. The chemical aspects as well as available bioactivity data are discussed and commented on, with particular attention to the underlying molecular mechanism(s).

Using a Bioactive Eremophila-Derived Serrulatane Scaffold to Generate a Unique Carbamate Library for Anti-infective Evaluations.

The known Eremophila microtheca-derived diterpenoid 3,7,8-trihydroxyserrulat-14-en-19-oic acid (1) was targeted for large-scale purification, as this bioactive plant compound has proven to be an attractive scaffold for semisynthetic studies and subsequent library generation. Compound 1 was converted to a selectively protected trimethyl derivative, 3-hydroxy-7,8-dimethoxyserrulat-14-en-19-oic acid methyl ester (2), using simple and rapid methylation conditions. The resulting scaffold 2 was reacted with a diverse series of commercially available isocyanates to generate an 11-membered carbamate-based library. The chemical structures of the 11 new semisynthetic analogues were fully characterized by spectroscopic and spectrometric analysis. All natural products and semisynthetic compounds were evaluated for their anthelmintic, antimalarial, and anti-HIV activities. Compound 3 was shown to elicit the greatest antiplasmodial activity of all compounds tested, with IC50 values of 4.6 and 11.6 μM against Plasmodium falciparum 3D7 and Dd2, respectively. Compound 11 showed the greatest inhibition of development to fourth-stage Haemonchus contortus larvae (L4) and induction of a skinny (Ski) phenotype (67.5% of nematodes) at 50 μM. Compound 7, which inhibited 59.0% of HIV production at 100 μg/mL, was the carbamate analogue that displayed the best antiviral activity.

Optimization of Composite Eco-Blocks Derived From Sawdust Ash and Plastic as an Alternative Aggregate

Plastic garbage circulating in bodies of water such as river streams, obstructing drainage canals, and massive piles of stinking waste are among the most indicative demonstrations of the Philippines rampant dissipation of waste in the environment. According to a 2015 report on plastic pollution by the Ocean Conservancy Charity and the McKinsey Centre for Business and Environment, the Philippines is the third-largest source of waste plastic that ends up in the ocean, after China and Indonesia. The Philippines discards around 2 million tons of plastic waste annually. Sawdust is a byproduct or waste product of the woodworking industry. Plastic is a material made up of a variety of synthetic or semi-synthetic organic compounds that are malleable and may be molded into solid things. Eco-blocks are eco-friendly bricks composed of recycled materials. The primary goal of this research is to create concrete blocks out of ground plastic wrappers and sawdust that has been burned to generate ash using alternative concrete aggregate. This research study may aid in the reduction of plastic waste and the preservation of the ecosystem. Each set included three types of concrete blocks: eco-blocks made from ground-up plastic cellophane, sawdust eco-blocks, and commercial hollow blocks. The Regional Office of the Department of Public Works and Highways examined the compression strength and wetness of eco-blocks. According to the findings, there is no discernible difference in durability between commercial hollow blocks and eco-blocks. When compared to grinded plastic cellophane eco-blocks and conventional hollow blocks, sawdust eco-blocks have a significant difference in terms of durability. The blocks have 9.69% less moisture than the limit of 45%, indicating a good grade block that fits the standards. As a result, eco-blocks manufactured from ground plastic cellophane and eco-blocks created from sawdust ash have the same potential and capability as commercial hollow blocks and are helpful concrete blocks when building structures.

Investigation of Antimicrobial Activity of Some Ethylparaben Hydrazide-Hydrazone Derivatives.

The development of antimicrobial molecules discussed with considerable achievement over the past decades provided many classes of semisynthetic or synthetic compounds. Resistance to many antimicrobial agents requires the discovery of novel molecules. In this study, ten ethylparaben hydrazide-hydrazone derivatives, the previously reported, were evaluated for their in vitro antibacterial and antifungal activities. The microbroth dilution method was used for the determination of the minimum inhibitory concentration (MIC) values of the novel molecules. The antimicrobial activities of the molecules were found in a wide range with MIC values of 2-256 μg/mL. The synthesized compounds showed good to moderate antimicrobial activity compared with the standards. Among the synthesized molecules, compound 3g showed the best antimicrobial activity at 2 μg/mL against Staphylococcus aureus strain (ATCC 29213). Ethylparaben hydrazide-hydrazone compounds in our study were found to have antimicrobial activities. Ethylparaben is currently used as an antibacterial agent and preservative for preparations. These studies are necessary since they detect the relationship between the substitutions and activity.

Biotransformation studies on bioactive compounds: 25 years of interesting research at the ICCBS

Biotransformation of natural, synthetic, and semi-synthetic compounds has emerged as a frontier branch of chemical sciences that is progressively being applied in numerous fields. In the present review, we have summarized our biotransformation studies on bioactive compounds from 1997 to 2022. Various microbial and plant cell cultures were used for biocatalytic structural transformations. We present here an overview of biotransformation of 53 compounds belonging to various classes of natural, synthetic, and semi-synthetic compounds, published in several leading journals. The structures of the resulting metabolites have been elucidated by detailed spectroscopic studies. Oxidation, reduction, dehydrogenation, chlorination, aromatization, methylation, demethylation, rearrangements, etc. were the main reactions that occurred during the biotransformation processes. Many of the biotransformed products exhibited interesting biological activities. Structural transformations in some cases have also led to improved pharmacokinetic profiles. This review is aimed to provide a focused account of extensive work carried out in our laboratories in this field, as well as the immense potential of biocatalytic transformations in organic chemistry.

Oudemansin and 9-methoxystrobilurin derivatives with antimalarial activity from cultures of the basidiomycete Favolaschia minutissima: assignments of the absolute configurations of the isoprene-derived units.

Five undescribed polyketide metabolites, oudemansins E (1), M (2), P (3), and Q (4), and 9-methoxystrobilurin I (5), were isolated from cultures of basidiomycete Favolaschia minutissima TBRC-BCC 19434. A γ-lactone derivative (6) of noroudemansin A (8), which was previously reported as a semisynthetic compound, was also isolated. The absolute configuration of the isoprene-derived moiety of the known cometabolite 9-methoxystrobilurin E (9) was determined to be 2'R,6'S by comparison of the experimental and calculated ECD data, which was correlated to the new derivative 1. These compounds exhibited antimalarial activity against Plasmodium falciparum K1 (multidrug-resistant strain). A putative minor natural product, namely 9-methoxystrobilurin P (13), was prepared by semisynthesis, which exhibited significant antimalarial activity (IC50 0.086 μM).

Natural Compounds as Non-Nucleoside Inhibitors of Zika Virus Polymerase through Integration of In Silico and In Vitro Approaches.

Although the past epidemic of Zika virus (ZIKV) resulted in severe neurological consequences for infected infants and adults, there are still no approved drugs to treat ZIKV infection. In this study, we applied computational approaches to screen an in-house database of 77 natural and semi-synthetic compounds against ZIKV NS5 RNA-dependent RNA-polymerase (NS5 RdRp), an essential protein for viral RNA elongation during the replication process. For this purpose, we integrated computational approaches such as binding-site conservation, chemical space analysis and molecular docking. As a result, we prioritized nine virtual hits for experimental evaluation. Enzymatic assays confirmed that pedalitin and quercetin inhibited ZIKV NS5 RdRp with IC50 values of 4.1 and 0.5 µM, respectively. Moreover, pedalitin also displayed antiviral activity on ZIKV infection with an EC50 of 19.28 µM cell-based assays, with low toxicity in Vero cells (CC50 = 83.66 µM) and selectivity index of 4.34. These results demonstrate the potential of the natural compounds pedalitin and quercetin as candidates for structural optimization studies towards the discovery of new anti-ZIKV drug candidates.

Dimethylmyricacene: An In Vitro and In Silico Study of a Semisynthetic Non-Camptothecin Derivative Compound, Targeting Human DNA Topoisomerase 1B.

Human topoisomerase 1B regulates the topological state of supercoiled DNA enabling all fundamental cell processes. This enzyme, which is the unique molecular target of the natural anticancer compound camptothecin, acts by nicking one DNA strand and forming a transient protein-DNA covalent complex. The interaction of human topoisomerase 1B and dimethylmyricacene, a compound prepared semisynthetically from myricanol extracted from Myrica cerifera root bark, was investigated using enzymatic activity assays and molecular docking procedures. Dimethylmyricacene was shown to inhibit both the cleavage and the religation steps of the enzymatic reaction, and cell viability of A-253, FaDu, MCF-7, HeLa and HCT-116 tumor cell lines.

Bioactive Extracts: Strategies to Generate Diversified Natural Product- Like Libraries

Abstract: Natural products have stimulated the interest of chemists owing to their abundant structural diversity and complexity. Indeed, natural products have performed an essential role, particularly in the cure of cancerous and infectious diseases, thereby providing medicinal researchers with several unexplored chemotypes for the innovation of new drugs. Fusion of chemical derivatization and combinatorial synthesis forms the basis of the concept of chemo diversification of plants. Diverse libraries of natural product analogs are constructed through existing biological and chemical approaches using unique schemes to expand natural product frameworks. This review aims to present several approaches employed to offer innovative opportunities to synthesize NP-inspired compound libraries. Reactive molecular fragments present in most natural products are chemically converted to chemically engineered extracts (CEEs) or semisynthetic compounds constituting distinct libraries. Bio-guided isolation for natural products required vital tools like reverse phase chromatography and bioautographic assays. Different established strategies from DTS, BIOS, CtD, FOS, FBDD to late-stage diversification facilitate the expansion of molecules with physicochemical properties. In particular, fragment-like natural products with novel skeletons may be used as preliminary points for chemical biology and medicinal chemistry programs with great capacity. In this review, we sum up how NPs have proven fruitful for the novel methodologies responsible for the diversification of complex natural products; therefore, it is worth going over the upcoming integration of natural products with combinatorial chemistry.

Development of Semisynthetic Apoptosis-Inducing Agents Based on Natural Phenolic Acids Scaffold: Design, Synthesis and In-Vitro Biological Evaluation.

A crucial target in drug research is magnifying efficacy and decreasing toxicity. Therefore, using natural active constituents as precursors will enhance both safety and biological activities. Despite having many pharmacological activities, caffeic and ferulic acids showed limited clinical usage due to their poor bioavailability and fast elimination. Therefore, semisynthetic compounds from these two acids were prepared and screened as anticancer agents. In this study, CA and FA showed very potent anticancer activity against Caco-2 cells. Consequently, eighteen derivatives were tested against the same cell line. Four potent candidates were selected for determination of the selectivity index, where compound 10 revealed a high safety margin. Compound 10 represented a new scaffold and showed significant cytotoxic activity against Caco-2. Cell-cycle analysis and evaluation of apoptosis showed that derivatives 10, 7, 11, 15 and 14 showed the highest proportion of cells in a late apoptotic stage.

Pterostilbene-isothiocyanate impedes RANK/TRAF6 interaction to inhibit osteoclastogenesis, promoting osteogenesis in vitro and alleviating glucocorticoid induced osteoporosis in rats

Prolonged glucocorticoid treatment often leads to glucocorticoid-induced osteoporosis (GIOP), a common iatrogenic complication. This study has explored the anti-osteoporotic potential of semi-synthetic compound, pterostilbene isothiocyanate (PTER-ITC) in GIOP rat model and bone formation potential in vitro. Dysregulated bone-remodelling leads to osteoporosis. PTER-ITC has shown anti-osteoclastogenic activity in vitro. However, its molecular target remains unidentified, which has been explored in this study through in silico and experimental approaches. Alizarin Red S and von-Kossa staining, and alkaline phosphatase (ALP) activity showed the osteogenic differentiation potential of PTER-ITC in pre-osteoblastic mouse MC3T3-E1 and human hFOB 1.19 cells, further, confirmed through the expressions of osteogenic markers at transcriptional (RT-qPCR) and translational (immunoblotting) levels. The anti-osteoclastogenic property of PTER-ITC was confirmed through inhibition of actin ring formation in mouse RAW 264.7 and human THP-1 macrophagic cells. Molecular docking and molecular dynamic simulation showed that PTER-ITC inhibited the crucial osteoclastogenic RANK/TRAF6 interaction, which was further confirmed biochemically through co-immunoprecipitation assay. Osteoporotic bone architecture [validated through scanning electron microscopy (SEM), X-ray radiography, and micro-computed tomography (µ-CT)], physiology (confirmed through compression testing, Young’s modulus and stress versus strain output) and histology (verified through hematoxylin-eosin, Alizarin Red S, von-Kossa and Masson-trichrome staining) of PTER-ITC-treated GIOP female Wistar rats were assuaged. Osteoporotic amelioration through PTER-ITC treatment was further substantiated through serum biomarkers, like, parathyroid hormone (PTH), ALP, calcium (Ca2+), Procollagen type I N-terminal propeptide (P1NP), and 25-hydroxy vitamin D. In conclusion, this study identifies the molecular target of PTER-ITC in impeding osteoclastogenesis and facilitating osteogenesis to ameliorate osteoporosis.

Identification and isolation of phytochemical constituents from the Syzygium cumini (L.) Skeels

The development of various drugs from medicinal plants are based on its phytochemical and pharmacological approaches for curing different diseases, therefore, various plants are recognized in the pharmaceutical industries for their broad structural diversity and wide range of pharmacological activities. These phytochemicals compounds are used as sources of direct medicinal agents or can serve as a raw material base for elaboration of more complex semi-synthetic chemical compounds. Since there is very minimal or no side effects, the need of looking inwards to search for herbal medicinal plants with the aim of validating the medicinal use and subsequently isolation and characterization of compounds becomes important which can be added to the potential list of drugs. The present study deals with the extraction of active compounds from the seeds of Jambolan plant and qualitative analysis of the phytochemicals using GCMS. The major constituents identified in the extract were gamma-sitosterol, cholest-4-ene-3-one, humulene, caryophyllene, alpha-santalol, campesterol, globulol, eicosane, azulene, trans-sesquisabinene, diosgenin, heneicosane, beta tocopherol, carotol etc. Many other compounds were also identified as considered as low level. Out of which gamma-sitosterol is the main phytochemical having functional group of OH, which may be responsible for reducing the level of glucose in blood in curing diabetes. This preliminary study gives an idea to isolate the major active constituents present in the seed of the plant and also helps to develop potential phar­macologically active compounds in therapeutic use of various ailments including diabetes.

Trisnor-Euphane-Type Triterpenoid and Other Constituents Isolated from Euphorbia tanquahuete Sessé & Moc.: Preparation and Cytotoxic Evaluation of Semisynthetic Derivatives of Euphol.

The natural compound 25,26,27-trisnor-3β-hydroxy-euphan-24-al (1) was isolated for the first time from the bioactive extract of the leaves of Euphorbia tanquahuete, together with the known compounds euphol, eupha-8,23-dien-3β,25-diol, lupeol, cycloeucalenol, β-sitosterol, squalene, and 1-octacosanol. The structure of the new compound was elucidated based on extensive analysis of spectroscopic data and by semisynthesis from euphol. The chemical modification of the alcohol at C3 and the side chain of euphol afforded seven derivatives (6–12). The cytotoxic activity of the natural and semisynthetic compounds evaluated against a panel of human cancer cell lines showed selectivity for certain cell lines and indicated that natural compound 1 and semisynthetic 8 were the most active against leukemia (K562) cell line.

New Anticancer Theobromine Derivative Targeting EGFRWT and EGFRT790M: Design, Semi-Synthesis, In Silico, and In Vitro Anticancer Studies.

Based on the pharmacophoric features of EGFR inhibitors, a new semisynthetic theobromine-derived compound was designed to interact with the catalytic pocket of EGFR. Molecular docking against wild (EGFRWT; PDB: 4HJO) and mutant (EGFRT790M; PDB: 3W2O) types of EGFR-TK indicated that the designed theobromine derivative had the potential to bind to that pocket as an antiangiogenic inhibitor. The MD and MM-GBSA experiments identified the exact binding with optimum energy and dynamics. Additionally, the DFT calculations studied electrostatic potential, stability, and total electron density of the designed theobromine derivative. Both in silico ADMET and toxicity analyses demonstrated its general likeness and safety. We synthesized the designed theobromine derivative (compound XI) which showed an IC50 value of 17.23 nM for EGFR inhibition besides IC50 values of 21.99 and 22.02 µM for its cytotoxicity against A549 and HCT-116 cell lines, respectively. Interestingly, compound XI expressed a weak cytotoxic potential against the healthy W138 cell line (IC50 = 49.44 µM, 1.6 times safer than erlotinib), exhibiting the high selectivity index of 2.2. Compound XI arrested the growth of A549 at the G2/M stage and increased the incidence of apoptosis.

Design, synthesis and cytotoxic evaluation of novel betulonic acid-diazine derivatives as potential antitumor agents.

With the purpose to improve antiproliferative activity, 26 new betulonic acid-diazine derivatives were designed and synthesized from betulinic acid. The anticancer activity of these semi-synthetic compounds was evaluated by MTT assay in both tumor cell lines and normal cell line. The results indicated that majority of new compounds exhibited improved antitumor activity compared with the parent compound betulonic acid. Compound BoA2C, in particular, had the most significant action with IC50 value of 3.39 μM against MCF-7 cells, while it showed lower cytotoxicity on MDCK cell line than cisplatin. Furthermore, we discovered that BoA2C strongly increased MCF-7 cell damage mostly by influencing arginine and fatty acid metabolism. In addition, the structure-activity relationships were briefly discussed. The results of this study suggested that the introduction of different diazines at C-28 could selectively inhibit different kinds of cancer cells and might be an effective way to synthesize potent anticancer lead compound from betulonic acid.

Identifikasi Senyawa Mdma dan Paracetamol dalam Sampel Urine Menggunakan Metode Kromatografi Lapis Tipis dan Kromatografi Gas – Spektrofotometri Massa (Gc-Ms)

MDMA (3,4-methylenedioximet amphetamine) is a semisynthetic compound derived from stimulant type amphetamine (ATS) which works by triggering the release of serotonin. Paracetamol (acetaminophen) is one type of drug that has an analgesic-antipyretic effect. MDMA analysis requires a relatively fast method, so the TLC method was chosen. The identification test was carried out using 3 chromatographic systems, namely methanol: ammonia TA (100:1.5 v/v), methanol: butanol TAF (60:40 v/v), and Toluene: acetone: ethanol: ammonia TAEA (45: 45: 7: 3v/v/v/v). The determination test was carried out using the TAEA system and MDMA was used as a standard. The results of the identification test showed that the sample contained MDMA through the Hrfc and spectrum approaches. Qualitative Analysis of Paracetamol Compounds (Acetaminophen) in Urine aims to analyze paracetamol compounds (acetaminophen) in urine qualitatively by using gas chromatography - mass spectrometry (GC-MS). Extraction of paracetamol in urine samples was carried out using ethyl acetate, which was then derivatized using BSTFA containing 1% TMCS and analyzed using gas chromatography – mass spectrometry (GC-MS). The results showed that urine samples at 1, 2, and 3 hours after consuming paracetamol gave positive results for acetaminophen-TMS while at 24, 168, and 720 hours after consumption they were negative.

A revised version of the Iwaoka’s assay: Application of hyphenated techniques

Assessing the effects of glutathione peroxidase (GPx)-like catalytic activities of natural, semi-synthetic, and synthetic compounds is nowadays well recognized of importance for the preliminary screening of potential anti-inflammatory, neuroprotective, and anti-cancer agents. To this aim the Iwaoka’s assay, relying on 1H NMR data recording, has been the most exploited test. In this short communication we propose an efficient and easy to perform methodology to accomplish the same process based on the application of hyphenated techniques like gas-chromatography coupled to mass spectrometry (GC-MS) and high-performance liquid chromatography with diode array detection (HPLC-DAD). The assay consisted in monitoring and quantifying the oxidation at different times of 1,4-dithiothreitol to 4,5-dihydroxy-1,2-dithiane in the presence of H2O2 and 2-phenyl-1,2-benzoselenazol-3(2H)-one (Ebselen) as the catalyst in EtOAc or MeOH as the solvents. The results we recorded by the application of both GC-MS and HPLC-DAD, showed that the GPx-like activity of Ebselen, used as the reference compound, can be effectively monitored in a time-course manner, and compare favorably to the NMR-based test.

Capability of MXene 2D material as an amoxicillin, ampicillin, and cloxacillin adsorbent in wastewater

Amoxicillin, ampicillin, and cloxacillin are three semi-synthetic antibiotic compounds that pollute wastewaters. Antibiotic compounds demonstrate resistance against conventional wastewater treatment methods; this can cause the development of some bacteria that can resist antibiotic compounds. Therefore, novel methods have been suggested for these contaminant treatments. Adsorption is an effective method to eliminate such contaminations. MXenes are 2D materials that can be used as adsorption elements due to their high surface area and chemical stability. This work applies three MXenes (Mn2C, Ti2C, and V2C) as removal agents for mentioned antibiotic compounds using molecular dynamic simulations (MD). According to the results of analyses, Ti2C exhibited the best performance among MXenes, which are appropriate materials for the adsorption of antibiotic compounds. It adsorbed 100%, 88%, and 44% of cloxacillin, amoxicillin, and ampicillin molecules, respectively. Also, it has been shown that functionalizing MXene using hydroxyl and amine groups results in more antibiotic adsorption intensity. Also, this work has shown that Ti2C is a reusable adsorbent. Finally, this work could develop the application of reusable MXenes in removing antibiotics from aqueous mediums.

A comprehensive review on chemistry and pharmacology of marine bioactives as antimetastatic agents

Metastasis by and large is responsible for the worldwide deaths associated with various types of cancers. The metastatic variant of cancer cells generated due to the cellular heterogeneity and abnormal activation of various signaling pathways in the tumor population leads to the progressive colonization of cancer cells in various organs. Over the years there has been a constant effort towards developing effective therapeutic strategies for the treatment and prevention of metastasis. The current conventional therapies have lacked efficacy due to the complex nature of metastasis involving multistep processes comprising tumor-tumor and tumor–extracellular matrix adhesion molecules, EMT, proteases, and tumor developing cell pathways. Albeit the exact mechanism of metastasis is somewhat still uncertain, there are a few recognized targets such as EMT markers, MMPs, serine proteases, microtubulin, angiogenic markers, and anoikis resistance, that have been identified as potential therapeutic targets for the inhibition of metastatic progression of cancer cells. Marine biodiversity offers unique chemical compounds due to the exposure to stressful environments for the discovery of novel bioactive compounds that are highly specific to these therapeutic targets. The review discusses various natural and semisynthetic compounds of marine origin having antimetastatic potential, focusing on the isolation, underlying mechanism of inhibition of multiple signaling pathways, and structural modification of isolated compounds for further development as drug candidates having superior clinical translation potential.

Chemical constituents from Diospyros fragrans Gürke (Ebenaceae)

A new naphtalenone derivative named fragranone, alongside seventeen known compounds: ten triterpenoids, one monoglycerol, one polyterpenoid, one carotenoid, two steroids and two polyols were isolated from the leaves and roots of Diospyros fragrans. Four semi-synthetic derivatives obtained from the acetylation and allylation of betulinic acid, allylation of ursolic acid and acetylation of vismiaefolic acid are also reported. The structures of the compounds were established using their MS and NMR spectral data. The chemotaxonomic relevance of the compounds is also discussed in this paper. The extracts, as well as the isolates and the semi-synthetic compounds were evaluated for their antibacterial and cytotoxic activities. The obtained results showed a moderate antibacterial activity for myrtifolic acid and the semi-synthetic compound betulinic acid acetate against Bacillus subtilis DSMZ 704 with a diameter zone of inhibition of 9 and 10 mm, respectively. Ursolic acid and corosolic acid exhibited a moderate cytotoxicity against human colorectal adenocarcinoma cells HT-29 and the cervix carcinoma cells KB-3-1 with inhibitory concentration 50 values of 34.4 and 50.9 μM for ursolic acid, and 16.5 and 14.6 μM for corosolic acid, respectively.