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The present study reports the biotransformation of an anabolic-androgenic steroid (AAS) drostanolone heptanoate (1) by using two microbial cultures, Beauveria bassiana, and Macrophomina phaseolina. Fermentation of 1 with B. bassiana yielded five new transformed products 2–6, while with M. phaseolina it afforded two new 7–8, and two known 9–10 metabolites. The main sites of hydroxylation in the steroidal skeleton of 1 were at C-5, C-7, C-11, C-14, C-15, and C-20, hydrolysis of the ester moiety at C-17, and reduction of the carbonyl group at C-3. The structures of the transformed products were determined by using mass, NMR, and other spectroscopic techniques.

Glomerella fusarioides-mediated structural modifications of steroidal anabolic drug, oxandrolone (1), yielded a new product 17β,11α-dihydroxy-17α-methylandrosta-2-oxa-4-ene-3-one (2). Similarly, Cunninghamella elegans-catalyzed transformation of a steroidal anti-epileptic drug ganaxolone (3) afforded a new metabolite 14α-hydroxy-5α-pregnan-1-ene-3,20-dione (4). Structures of new metabolites 2 and 4 were deduced via 1D-, and 2D-NMR, HREI-, HRFAB-MS, and IR spectroscopic techniques. New derivative 2 showed a remarkable anti-aromatase activity with an IC50 = 0.6 ± 0.005 μM, when compared to substrate 1 (IC50 = 0.808 ± 0.07 μM), and standard anti-cancer drug exemestane (IC50 = 0.232 ± 0.031 μM). Ganaxolone (3) (IC50 = 13.76 ± 2.00 μM) also showed a good activity against human aromatase enzyme, while its derivative 4 was found to be inactive. Inhibition of aromatase enzyme is a key approach in the treatment of estrogen positive breast cancers. Compounds 1-4 were non-cytotoxic to 3T3 cell line (mouse fibroblast).

Aim: To evaluate the Clinico-Demographic variables in patients of Oral Submucous Fibrosis Study Design: Descriptive Cross Sectional Place and Duration of Study: Department of Oral and Maxillofacial Surgery, Liaquat Medical University Hospital from December 2017 to February 2019. Methodology: The recruitment of patients was done after the clinical diagnosis of oral sub mucous fibrosis (OSMF) patients. The demographic information and associated factors were recorded on the proforma. Mouth opening (MO) was measured between upper and lower central incisors with vernier caliper. Burning sensation (BS) and pain were measured using Visual Analog Scale (VAS). The data were analyzed by SPSS Version-16. Results: Male and female were (66%) and (34%) respectively. The mean age was 41.04±11.24. The frequency of gutka usage was 44% and 43% followed by betel nut as 21% and 23% in functional stages as per Inter Incisal Mouth Opening (IIMO-2) and (IIMO-3) respectively. The BS was shown as severe 49% and 40% followed by moderate as 32% and 37% in functional stages IIMO-2 and IIMO-3 respectively whereas pain was shown as severe 82% and 18% and as moderate 63% and 37% in functional stage M2 and M3 respectively showed statistically significant relationship (p=0.041). Conclusion: Males were more affected and middle aged patients were more involved. Majority of patients were using gutka and had 3rd functional stage of mouth opening. The burning sensation and pain were the most common clinical complains. There was significant relationship of functional stages with pain.

A new pentacyclic triterpene 3-O-β-(E)-(4-O-acetylferuloyl)-lupeol (1) possessing an unusual (E)-acetylferuloyl moiety at C-3 and a new bicoumarin 7,7′-dimethoxy-6,6′-dicoumarinyl ether (2) were isolated from the liana Landolphia lucida K. Schum, along with fourteen previously known compounds 3-16, where methandriol dipropionate (3) and 2,3-bis-(4-hydroxy-3-methoxy-benzyl)-dimethyl- succinate (5) were obtained for the first time from natural sources. The structures of the new compounds were established on the basis of extensive 1D and 2D NMR spectroscopy, and HRMS data analyses. The absolute configuration of 1 was determined by circular dichroism (CD) spectroscopy. Furthermore, compounds 1 and 2 had exhibited a significant antibacterial activity against Escherichia coli (ATCC 25922) with MIC values of 2.3 μM and 4.6 μM, respectively; while compounds 4 and 5 showed antiglycation and α-glucosidase inhibitory activities.

Kadsura heteroclita Roxb. Craib. (Schisandraceae), is a vine plant mainly distributed in southwest part of China. A new dibenzocyclooctadiene lignan, kadsulignan W (1), along with eleven known lignans (2-12) were isolated from chloroform soluble fraction of stems of Kadsura heteroclita. The structure of new lignan was elucidated by extensive spectroscopic techniques, namely one- and two-dimensional NMR spectroscopy, and HRESI-MS analysis. The absolute configuration of the biphenyl ring in the new dibenzocyclooctadiene lignan was discerned by circular dichroism (CD) spectroscopy. Antioxidative effects of these compounds were evaluated on human isolated neutrophils, and compounds 5, 8, 9, and 10 were found to be strongly active with the IC50 of 36.68, 34.41, 35.97, and 33.65 µM, respectively. Furthermore, compound 8 was also found to be cytotoxic against human gastric cancer cells (BGC 823), and human cervical cancer cell lines (HeLa) with the IC50 values of 11.0, and 23.8 µM, respectively.

Candida albicans is the causative agent of candidiasis in immunocompromised and diseased individuals. The current study was designed to evaluate the antifungal activity of Trachyspermum ammi (L.) Sprague seeds ethanolic extract and hexanes fraction against Candida albicans, both in-vitro and in-vivo. The minimal inhibitory concentration of hexanes fraction was found to be 225 μg/mL, as compared to the standard drug amphotericin B (200 μg/mL). For the treatment of cutaneous candidiasis in BALB/c mice model, the extract and fraction containing ointment was topically applied on flank of mice at various concentrations, and 90–100% recovery in mice was observed which was better than the standard drug, clotrimazole. The GC/MS analysis of hexanes extract indicated the presence of three major components, including (43.91%), O-cymene (25.53%), and γ-terpinene (22.64%). The results showed that T. ammi possess potential antifungal effect, and can be used for the development of novel antifungal agents after further pre-clinical and clinical trials.

Graphical abstract, Seven new derivatives, 6α-hydroxy-1-methyl-3-oxo-5α-androst-1-en-17-yl acetate (2), 6α,17β-dihydroxy-1-methyl-3-oxo-5α-androst-1-en (3), 7β-hydroxy-1-methyl-3-oxo-5α-androst-1-en-17-yl acetate (4), 15β,20-dihydroxy-1-methyl-3-oxo-5α-androst-1-en-17-yl acetate (5), 15β-hydroxy-1-methyl-3-oxo-5α-androst-1-en-17-yl acetate (6), 12β,17β-dihydroxy-1-methyl-3-oxoandrosta-1,4-dien (11), and 7β,15β,17β-trihydroxy-1-methyl-3-oxo-5α-androst-1-en (14), along with six known metabolites, 17β-hydroxy-1-methyl-3-oxoandrosta-1,4-dien (7), 17β-hydroxy-1-methyl-3-oxo-5α-androst-1-en (8), 17β-hydroxy-1-methyl-3-oxo-5β-androst-1-en (9), 1-methyl-5β-androst-1-en-3,17-dione (10), 1-methyl-3-oxoandrosta-1,4-dien-3,17-dione (12), and 17β-hydroxy-1α-methyl-5α-androstan-3-one (13) of metenolone acetate (1), were synthesized through whole-cell biocatalysis with Rhizopus stolonifer, Aspergillus alliaceous, Fusarium lini, and Cunninghamella elegans. Atamestane (12), an aromatase inhibitor, was synthesized for the first time via F. lini-mediated transformation of 1 as the major product. Hydroxylation, dehydrogenation, and reduction were occurred during biocatalysis. Study indicated that F. lini was able to catalyze dehydrogenation reactions selectively. Structures of compounds 1–14 were determined through NMR, HRFAB-MS, and IR spectroscopic data. Compounds 1–14 were identified as non-cytotoxic against BJ human fibroblast cell line (ATCC CRL-2522). Metabolite 5 (81.0 ± 2.5%) showed a potent activity against TNF-α production, as compared to the substrate 1 (62.5 ± 4.4%). Metabolites 2 (73.4 ± 0.6%), 8 (69.7 ± 1.4%), 10 (73.2 ± 0.3%), 11 (60.1 ± 3.3%), and 12 (71.0 ± 7.2%), also showed a good inhibition of TNF-α production. Compounds 3 (IC50 = 4.4 ± 0.01 µg/mL), and 5 (IC50 = 10.2 ± 0.01 µg/mL) showed a significant activity against T-cell proliferation. Identification of selective inhibitors of TNF-α production, and T-cell proliferation is a step forward towards the development of anti-inflammatory drugs.

The microbial transformation of anabolic androgenic steroid mestanolone (1) with Macrophomina phaseolina and Cunninghamella blakesleeana has afforded seven metabolites. The structures of these metabolites were characterized as 17β-hydroxy-17α-methyl-5α-androsta-1-ene-3,11-dione (2), 14α,17β-dihydroxy-17α-methyl-5α-androstan-3,11-dione (3), 17β-hydroxy-17α-methyl-5α-androstan-1,14-diene-3,11-dione (4), 17β-hydroxy-17α-methyl-5α-androstan-3,11-dione (5), 11β,17β-dihydroxy-17α-methyl-5α-androstan-1-ene-3-one (6), 9α,11β,17β-trihydroxy-17α-methyl-5α-androstan-3-one (7), and 1β,11α,17β-trihydroxy-17α-methyl-5α-androstan-3-one (8). All the metabolites, except 5 and 6, were identified as new compounds. Substrate 1 (IC50 = 27.6 ± 1.1 μM), and its metabolites 2 (IC50 = 19.2 ± 2.9 μM) and 6 (IC50 = 12.8 ± 0.6 μM) exhibited moderate cytotoxicity against the HeLa cancer cell line (human cervical carcinoma). All metabolites were noncytotoxic to 3T3 (mouse fibroblast) and H460 (human lung carcinoma) cell lines. The metabolites were also evaluated for immunomodulatory activity, and all were found to be inactive.

Synthesis of pyrazole-3-carboxylic acid was progressed via two different protocols, one of which is solid state. Pyrazole-3-carboxylic acid was converted into different derivatives such as ester, urea, amide and nitrile. The amide compound was converted to nitrile using SOCl2 and DMF. Solid state heating of carboxylic acid gave decarboxylated product. Cyclization of tetra-substituted pyrazole with hydrazines resulted in pyrazolopyridazinones. The antimicrobial activities of the synthesized pyrazole derivatives against Bacillus cereus, Escherichia coli, Micrococcus luteus, Staphylococcus aureus, and Saccharomyces cerevisiae were evaluated. One of the pyrazole derivatives which possess nitro group showed antimicrobial activity in only B. cereus, a Gram-positive bacteria, with an MIC of 128 μg/mL.

Picrotoxinin (1), a stable natural neurotoxin containing a highly oxygenated polycyclic rigid compound, was first isolated from berries of Anamirta cocculus (L.) Wight & Arn. (formerly known as Menispermum cocculus). The present work was aimed to study the modification of the complex polycyclic structure of picrotoxinin (1) by using microbial transformation. Initially various fungi, such as Macrophomina phaseolina, Cunninghamella blakesleeana, Aspergillus flavus, Aspergillus niger, Cephalosporium aphidicola, and Fusarium lini were screened for their ability to modify the structure of 1. Only one fungus Macrophomina phaseolina was able to catalyze the structural modification of picrotoxinin (1). The subsequent whole cell catalysis produced an intramolecular trans-esterified product 2. The structure of the transformed product was deduced by spectroscopic, and single-crystal X-ray diffraction analyses. A comparative study on convulsant activity of picrotoxinin (1) and its metabolite 2 was conducted in mice. Interestingly, metabolite 2 showed a delayed convulsant activity, as compared to the compound 1.

Objective: To investigate the changes in levels of C-reactive protein (CRP) and hematological parameters among smokeless tobacco (SLT) users. Methods: A comparative cross-sectional study was conducted at the community level in the coastal districts of Sindh province namely Badin, Thatta, and Sujawal from January 2017 to December 2019. The CRP and hematological parameters were evaluated by well-established methods among SLT and non-SLT users. Results: There was a statistically significant difference between SLT users (mean CRP = 0.77) versus non-users (mean CRP = 0.18), p =

Phytochemical investigation on the roots of Kadsura coccinea led to the isolation five previously unknown dibenzocyclooctadiene lignans, named heilaohusuins A-E (1–5). Their structures determined by NMR spectroscopy, HR-ESI-MS, and ECD spectra. Hepatoprotection effects of a series of dibenzocyclooctadiene derivatives (1–68) were investigated against acetaminophen (APAP) induced HepG2 cells. Compounds 2, 10, 13, 21, 32, 41, 46, and 49 showed remarkable protective effects, increasing the viabilities to > 52.2% (bicyclol, 52.1 ± 1.3%) at 10 μM. The structure–activity relationships (SAR) for hepatoprotective activity were summarized, according to the activity results of dibenzocyclooctadiene derivatives. Furthermore, we found that one new dibenzocyclooctadiene lignan heilaohusuin B attenuates hepatotoxicity, the mechanism might be closely correlated with oxidative stress inhibition via activating the Nrf2 pathway.

Ethnopharmacological relevance Schefflera is the largest genus in the family Araliaceae, which contains 602 known species indigenous to Asia, Africa, and the southwest Pacific region, several of which are used in traditional medicine. Aim of the review: The review discusses current knowledge of the traditional uses, phytochemistry, and biological activities of Schefflera species, to assess the medicinal potential of this genus. Materials and methods The literature were explored using the keyword “Schefflera” in SciFinder®, Google Scholar®, and PubMed® databases. The taxonomy of all reported plants was authenticated using “The Plant List”. Additional data on traditional uses was obtained from secondary references including books and online resources. Results Fourteen species were documented as traditional medicines in China, India, Vietnam, Thailand, and Indonesia, specifically to manage rheumatism, pain, and trauma. Other species are used in the treatment of liver disorders, skin conditions, respiratory infections, cancer, diarrhea, malaria, paralysis, and many other conditions. The main phytochemical constituents identified were triterpenoids and saponins, with sesquiterpenes, phenylpropanoids, and lignans. Pharmacological properties of extracts and pure isolated compounds included analgesic, anti-inflammatory, anticancer, hypoglycemic, antimicrobial, hepatoprotective, neuroprotective, antimalarial, and antiallergic effects. Conclusion The reported biological activities of Schefflera species support their traditional uses, although the available data, even for medicinal species, was limited. Reports of chemical constituents or biological activities could be found for only about 20 species, but suggest that further investigation of efficacy and safety of the largely unexplored genus Schefflera is necessary.

A new steroidal alkaloid, michainine (1), was isolated from Fritillaria michailovskyi Fomin, along with nine known compounds 2–10 of different classes, including ribonucleoside, steroids, and fatty acids, which were isolated for the first time from this plant. Their structures were elucidated through extensive spectroscopic techniques, as well as by comparing the data in the literature. Furthermore, the dichloromethane fraction of F. michailovskyi showed a positive butyrylcholinesterase inhibitory activity, along with non-cytotoxicity against 3T3 cell line.

Rice (Oryza sativa L.) is one of the most important crops in the world, providing staple food for approximately half of the world’s population. Globally, the widely cultivated varieties of rice are Oryza glaberrima (Steudel) and Oryza sativa (L.). Asia produces approximately 90% of the total world’s rice (nearly 640 million tons) where the major contributors are China, India, and Pakistan. Approximately 3.5 billion people rely on rice for 20% of their daily calorie intake. The major obstacles to wheat and rice cultivations include various physical and chemical parameters including excessive soil tillage; soils with low carbon (C), zinc (Zn), potassium (K); and inefficient use of soil nitrogen (N). Problems such as iron, phosphorus, and zinc deficiency or excess aluminum, iron, and salts in the soil have limited rice land in Asia by about 50 M ha. Modern agricultural systems use various plant varieties developed by the conventional breeding system, which has resulted in a significant increase in crop yields, specifically cereals. Development of effective gene transfer mechanisms in combination with mixed “omics” technologies has promoted knowledge of plant physiology and biochemistry for adaptive responses to adverse environmental conditions by recognizing the main molecular players regulating these responses. This chapter discusses how genetic engineering in rice has made it possible to survive in nutrient-deficient soil, with high yield.

A series of benzoxazinones 1 – 28 were synthesized via reaction of anthranilic acid with various substituted benzoyl chlorides in the presence of triethylamine in chloroform. Compounds 1 – 18 showed a good inhibition of α -chymotrypsin with IC 50 ± SEM values between 6.5 and 341.1 μM. Preliminary structure-activity relationships studies indicated that the presence of substituents on benzene ring reduces the inhibitory potential of benzoxazinone. Also the increased inhibitory potential due to fluoro group at phenyl substituent was observed followed by chloro and bromo substituents. Compounds with strong electron donating or withdrawing groups on phenyl substituent, showed a good inhibitory potential at ortho > meta > para position. Kinetics studies showed diverse types of inhibition, except uncompetitive-type inhibition. The Ki values ranged between 4.7 and 341.2 μM. Interestingly, most of these compounds were non-cytotoxic to 3T3 cell line at 30 μM, except compounds 6 , 14 and 15 . Competitive inhibitors of chymotrypsin are like to inhibit other α -chymotrypsin-like serine proteases due to structural and functional similarities between them. The inhibitors identified during the current study deserve to be further studied for their therapeutic potential against abnormalities mediated by chymotrypsin or other serine protease.

Honey is synthesized from flower nectar and it is famous for its tremendous therapeutic potential since ancient times. Many factors influence the basic properties of honey including the nectar-providing plant species, bee species, geographic area, and harvesting conditions. Quality and composition of honey is also affected by many other factors, such as overfeeding of bees with sucrose, harvesting prior to maturity, and adulteration with sugar syrups. Due to the complex nature of honey, it is often challenging to authenticate the purity and quality by using common methods such as physicochemical parameters and more specialized procedures need to be developed. This article reviews the literature (between 2000 and 2016) on the use of analytical techniques, mainly NMR spectroscopy, for authentication of honey, its botanical and geographical origin, and adulteration by sugar syrups. NMR is a powerful technique and can be used as a fingerprinting technique to compare various samples.

In the present work, we reported the triterpenoids isolated from n-butanol fraction of Kadsura heteroclita which is a Tujia ethnomedicine with trivial name “Xuetong”. This effort resulted in the isolation of six unpresented triterpenoids xuetongsu A-F (1–6), along with five known triterpenoids (7–11). The structures of the reported compounds were established on the 1D, and 2D NMR and HRESIMS spectra, along with CD spectroscopic analysis. Moreover, the absolute stereochemistry of compound 7 was determined by X-ray diffraction analysis. Antioxidant and cytotoxic activities were evaluated for all isolated compounds, compound 7 shown weak cytotoxic activity against HL-60 with IC50 value of 50.0 μM.

In the present work, we take advantage of the characteristic NMR signal (δC-10 = 96.0–99.9) for guiding the isolation of schinortriterpenoids (SNTs) from n-butanol fraction of stems of Kadsura heteroclita which is a Tujia ethnomedicine with trivial name “Xuetong”. This effort resulted in the identification of three unreported 3,4:9,10-disecocycloartane triterpenoids xuetongdilactones A-C and three undescribed SNTs xuetongdilactones D-F, along with two known SNTs, namely, wuweizidilactone B and micrandilactone B. The structures of the unreported compounds were established based on 1D, and 2D NMR, HRESIMS, and ECD spectroscopic data analysis. The absolute stereochemistry of xuetongdilactone A was determined by X-ray diffraction analysis along with ECD calculation. The antioxidant and cytotoxic activities were evaluated for all the isolated compounds.

Binglang, the fruit of Areca catechu L, has a long history as an important Chinese herbal medicine. Two new alkaloids (1 and 2), along with forty-one known compounds (3–43) were isolated from the dried fruit of Areca catechu L. The structures were elucidated on basis of the IR, UV, MS and 1D, 2D NMR spectroscopic data. Compounds 26 and 33 showed weak cytotoxicity against human gastric cancer cell line (BGC-823) with IC50 of 15.91 μM and 20.13 μM, respectively.

As part of our continual efforts to exploit &lsquo, Tujia Ethnomedicine&rsquo, for their pharmacophoric functionalities, we herein investigated Kadsura heteroclita collected from a deep Wulin mountain area in northern Hunan province. The current study resulted in the isolation of three new sesquiterpenes: 6&alpha, 9&alpha, 15-trihydroxycadinan-4-en-3-one (1), (+)-3,11,12-trihydroxycalamenene (2), (&ndash, )-3,10,11,12-tetrahydroxy-calamenene (3), along with four known sesquiterpenes (4&ndash, 7), and a cytochalasin H (8). Their chemical structures were elucidated by 1D-, and 2D-NMR spectroscopy, and HRESI-MS, CD spectrometry. The antioxidant, and cytotoxic activities of the compounds were evaluated. Compound 8 exhibited a strong antioxidant effect with an IC50 value of 3.67 &micro, M on isolated human polymorphonuclear cells or neutrophils.

Three new metabolites were obtained on incubation of androgenic steroid mesterolone ( 1 ) with Cunninghamella blakesleeana . These metabolites were identified as 1α-methyl-11 β ,14α,17β-trihydroxy-5α-androstan-3-one ( 2 ), 1α-methyl-7 β ,17 β -dihydroxy-5α-androstan-3-one ( 3 ), and 1α-methyl,17 β -hydroxy-5α-androstan-3,7-dione ( 4 ). During this study, hydroxylation at C-11, C-14, and C-15, and oxidation at C-7 of substrate 1 were observed. β -Hydroxylation at C-11 is a rather unique transformation by C. blakesleeana , as α-hydroxylation is reported to be catalyzed by most of the other microorganisms.

A library of benzimidazole derivatives 1-20 were synthesized, and studied for their α-chymotrypsin (α-CT) inhibitory activity in vitro. Kinetics and molecular docking studies were performed to identify the type of inhibition. Compound 1 was found to be a good inhibitor of α-chymotrypsin enzyme (IC50=14.8±0.1μM, Ki=16.4μM), when compared with standard chymostatin (IC50=5.7±0.13μM). Compounds 2-8, 15, 17, and 18 showed significant inhibitory activities. All the inhibitors were found to be competitive inhibitors, except compound 17, which was a mixed type inhibitor. The substituents (R) in para and ortho positions of phenyl ring B, apparently played a key role in the inhibitory potential of the series. Compounds 1-20 were also studied for their cytotoxicity profile by using 3T3 mouse fibroblast cells and compounds 3, 5, 6, 8, 12-14, 16, 17, 19, and 20 were found to be cytotoxic. Molecular docking was performed on the most active members of the series in comparison to the standard compound, chymostatin, to identify the most likely binding modes. The compounds reported here can serve as templates for further studies for new inhibitors of α-chymotrypsin and other chymotrypsin-like serine proteases enzymes.

Microbial transformation of 6-dehydroprogesterone (1) with Aspergillus niger yielded three new metabolites, including 6β-chloro-7α,11α-dihydroxypregna-4-ene-3,20-dione (2), 7α-chloro-6β,11α-dihydroxypregna-4-ene-3,20-dione (3), and 6α,7α-epoxy-11α-hydroxypregna-4-ene-3,20-dione (4), and two known metabolites; 6α,7α-epoxypregna-4-ene-3,20-dione (5), and 11α-hydroxypregna-4,6-diene-3,20-dione (6). Compounds 2, and 3 contain chlorohydrin moiety at C-6, and C-7, respectively. The biotransformation of 1 with Gibberella fujikuroi yielded a known compound, 11α,17β-dihydroxyandrosta-4,6-dien-3-one (7).

Bletilla striata belongs to the family Orchidaceae, and it is mainly distributed in East Asia. The tubers of B. striata have been utilized in Traditional Chinese Medicine for various ailments, such as hematemesis, tuberculosis, malignant ulcers, hemorrhoids, traumatic bleeding, and chapped skin. Phytochemical investigation on B. striata has resulted in the identification of 192 monomeric compounds, including bibenzyls, phenanthrene derivatives, triterpenoids and its saponins, steroids and its saponins, malic acid derivatives, and anthocyanins. Moreover, B. striata polysaccharide is another typical chemical constituent of this plant. Pharmacology studies have shown that the plant possesses wound healing, antimicrobial, anticancer, antioxidative, and antiviral activities. This review aims to provide the latest and comprehensive information on chemical constituents, pharmacological activities, and quality control of B. striata and to identify future research needs.

Biotransformation of a synthetic progestonic hormone dydrogesterone (1), C21H28O2, with a plant pathogenic fungus Macrophomina phaseolina yielded two new 2 and 3, and a known 4 metabolites. These analogues were identified as, 3β,11α-dihydroxy-5β,9β,10α-pregna-7-ene-6,20-dione (2), 15β-hydroxy-9β,10α-pregna-4,6-diene-3,20-dione (3), and 8α-hydroxy-9β,10α-pregna-4,6-diene-3,20-dione (4). Major structural changes were observed in metabolite 2. New metabolite 3 showed anti-inflammatory potential, and was found to be the potent inhibitor of intracellular reactive oxygen species (ROS) from whole blood phagocytes (IC50 = 4.2 ± 0.3 μg/mL), as compared to standard drug Ibuprofen (IC50 = 11.2 ± 1.9 μg/mL). The metabolites 2, 3, and 4 were found to be non-toxic to NIH-3T3 (CRL-1658) normal cell line. This indicated anti-inflammatory potential of resulting metabolites.

Oral cancer is one of the major cancer types, which has increased sustainably in Southeast Asian countries due to the extensive use of a variety of tobacco and betel nut products. The current study is focused on developing an easy, efficient and cost-effective method for plasma profiling of oral cancer patients and tobacco users in order to have a progressive picture towards oral cancer. For this purpose, the profiling of 147 plasma samples including 67 oral cancer patients' samples, 60 “niswar” (a dipping tobacco product) user samples, and 20 healthy controls using attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR), and chemometric analysis was carried out. Fingerprint region (500–1500 cm−1) of all three groups showed interesting variations in peaks pattern. From these observations, height ratios of two bands H1646/H1550 and H1080/H1024 with p value of 2.01 × 10–6 and 8.39 × 10–7, respectively, showed a pattern between healthy to oral cancer and “niswar” user samples. Chemometric analysis of the data showed a clean separation among the groups. PLS-DA and OPLS-DA models provided 87.7% and 89.5% classification rate, respectively. Area under the curve (AUC) for healthy control, oral cancer and “niswar” users were found to be 0.97, 0.95 and 0.92%, respectively. The results of the present study indicate that FT-IR spectroscopy, in conjunction with chemometric data, can be effectively used for the preliminary differentiation of plasma samples of oral cancer patients, “niswar” users and control samples of healthy persons.

Anabolic steroids are frequently misused for performance enhancement during sports competitions. One of the major bottlenecks in the confident analysis of steroids and their metabolites is the non-availability/cost of standard reference compounds. The study objective was to identify the common metabolites of prohibited anabolic steroids that are produced in both fungi and human and thus can be synthesized in bulk using fungal cultures. Mesterolone is used as a case study. The study was conducted in three steps; we first studied the fungal transformation of mesterolone. In the second step, these metabolites were used as references to detect in human urine after the oral use of mesterolone using LC-ESI-QqQ-MS/MS. In the third step, 12 fungal cultures were screened to evaluate their potential to produce reference markers. This led to the detection of two metabolites, 6α-hydroxymesterolone (M1) and 7α-hydroxymesterolone (M2) that were found to be common in both, fungal cultures and human urine samples. Moreover, Rhizopus stolonifer and Beauveria bassiana can be considered as good candidates to produce M1 and M2 metabolites, respectively. This approach can be employed for the synthesis of marker compounds of other prohibited anabolic steroids thus can be detected efficiently during national and international sports competitions.

We provide a comprehensive and updated review on the effects of elevation and climatic factors on distribution of sand fly (Diptera: Psychodidae) vectors of cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) across Pakistan. Our study was undertaken in view of the increasing risk of leishmaniasis, particularly resulting from climatic deviations and political instability in the region. Literature (published and unpublished) on suspected vectors of CL (Phlebotomus sergenti Parrot and Phlebotomus papatasi Scopoli) and VL (Phlebotomus major Yakimoff and Schokhor and Phlebotomus hindustanicus Theodor) was collected, sorted, and utilized in geospatial analysis. P. papatasi and P. sergenti co-occurred in majority of the referenced localities and were generally distributed toward the western and southern parts across a wide range of elevation, whereas P. major and P. hindustanicus were limited to high elevation in cool and humid northern areas of Pakistan. Conversely P. papatasi and P. sergenti exploited diverse ecological settings across the country, being particularly abundant in warm/hot and arid regions.

Background Multidrug resistance (MDR) is a major challenge in the treatment of infectious diseases. The MDR in urinary tract infection causing bacteria, such as Escherichia coli, has made treatment of UTI very difficult. Objective The aims of the current study were to synthesize a library of harmaline derivatives, and to evaluate their activity against various strains of multi-drug resistance (MDR) E. coli. Method Harmaline derivatives were synthesized by the reaction of harmaline (1) with various acid halides and anhydrides. These compounds were subjected to susceptibility determination by in vitro MTT assay. The changes in morphology of the bacterial cells after the treatment with harmaline (1) and its new derivatives 2 and 3 were studied through scanning electron, atomic force and fluorescence microscopy. Effect of harmaline and its derivatives in the production of Reactive Oxygen Species (ROS) in MDR E. coli was assessed through lucigenin chemiluminescence assay. Results The selected compounds assisted the fluorescently labeled dye DiBAC4 (3) to bind to the lipid rich intra-cellular entities, and thus produced a sharp green fluorescence by easily penetrating into the compound-induced depolarized membrane of MDR E. coli. These compounds have also triggered significant generation of ROS from bacterial cells as compared to the conventional antibiotics. The current study demonstrated that harmaline (1), and its derivatives 2 and 3 were identified as anti-MDR agents against MDR strains of E. coli. Antibacterial effect of compounds 1-3 on MDR E. coli is possibly due to membrane depolarization due to ROS-induced damage to the bacterial cell membrane. Conclusion Harmaline and its derivatives were identified as anti-MDR agents against various highly resistant and Pakistani MDR clinical isolates of E. coli. These discovered compounds may serve as the leads for further studies towards the development of treatment against the infection caused by MDR E. coli.

Aims The emergence of multidrug-resistant (MDR) Staphylococcus aureus is a challenge for the treatment of infections. We report here the antimicrobial activity of artonin I against MDR Staph. aureus, its mechanism of reversal of resistance and synergistic effects by combinational therapy. Methods and Results Artonin I, a flavonoid obtained from Morus mesozygia Stapf., inhibited the bacterial efflux pump and induced depolarization of the cell membrane. To study the dose-dependent production of reactive oxygen species in MDR cells by artonin I, lucigenin chemiluminescence assay was employed. Reversal of multidrug resistance by artonin I, in combination with antibiotics, was measured by a fractional inhibitory concentration index assay. The effect of artonin I on ultrastructural features was studied by microscopy. Artonin I increased the penetration of ethidium bromide by blocking the efflux mechanism. It also helped anionic probe DiBAC4 (3) to bind with the lipid-rich cellular components by causing depolarization of the cell membrane. Artonin I reversed multidrug resistance and increased the susceptibility of existing antibiotics by lowering their minimum inhibitory concentrations (MICs). Conclusions Artonin I was identified both as a new antibacterial agent and a helper molecule to potentiate the action of otherwise inactive antibiotics. Significance and Impact of the Study Artonin I can be developed as potential antimicrobial and resistance reversal agent.

Biotransformation of the anabolic steroid dianabol (1) by suspended-cell cultures of the filamentous fungi Cunninghamella elegans and Macrophomina phaseolina was studied. Incubation of 1 with C. elegans yielded five hydroxylated metabolites 2–6, while M. phaseolina transformed compound 1 into polar metabolites 7–11. These metabolites were identified as 6β,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (2), 15α,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (3), 11α,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (4), 6β,12β,17β-trihydroxy-17α-methylandrost-1,4-dien-3-one (5), 6β,15α,17β-trihydroxy-17α-methylandrost-1,4-dien-3-one (6), 17β-hydroxy-17α-methylandrost-1,4-dien-3,6-dione (7), 7β,17β,-dihydroxy-17α-methylandrost-1,4-dien-3-one (8), 15β,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (9), 17β-hydroxy-17α-methylandrost-1,4-dien-3,11-dione (10), and 11β,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (11). Metabolite 3 was also transformed chemically into diketone 12 and oximes 13, and 14. Compounds 6 and 12–14 were identified as new derivatives of dianabol (1). The structures of all transformed products were deduced on the basis of spectral analyses. Compounds 1–14 were evaluated for β-glucuronidase enzyme inhibitory activity. Compounds 7, 13, and 14 showed a strong inhibition of β-glucuronidase enzyme, with IC50 values between 49.0 and 84.9 μM.

Natural products continue to serve as an important source of novel drugs since the beginning of human history. High-throughput techniques, such as MALDI-MS, can be techniques of choice for the rapid screening of natural products in plant materials. We present here a fast and reproducible matrix-free approach for the direct detection of UV active metabolites in plant materials without any prior sample preparation. The plant material is mechanically ground to a fine powder and then sieved through different mesh sizes. The collected plant material is dispersed using 1 μL solvent on a target plate is directly exposed to Nd:YAG 335 nm laser. The strategy was optimized for the analysis of plant metabolites after study of the different factors affecting the reproducibility and effectiveness of the analysis, including particle sizes effects, types of solvents used to disperse the sample, and the part of the plant analyzed. Moreover, several plant species, known for different classes of metabolites, were screened to establish the generality of the approach. The developed approach was validated by the characterization of withaferin A and nicotine in the leaves of Withania somnifera and Nicotiana tabacum, respectively, through comparison of its MS/MS data with the standard compound. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) techniques were used for the tissue imaging purposes. This approach can be used to directly probe small molecules in plant materials as well as in herbal and pharmaceutical formulations for fingerprinting development.

Urease belongs to a family of highly conserved urea-hydrolyzing enzymes. A common feature of these enzymes is the presence of two Lewis acid nickel ions and reactive cysteine residue in the active sites. In the current study we examined a series of biscoumarins1–10for their mechanisms of inhibition with the nickel containing active sites of Jack bean andBacillus pasteuriiureases. All these compounds competitively inhibited Jack bean urease through interaction with the nickel metallocentre, as deduced from Michaelis-Menten kinetics, UV-visible absorbance spectroscopic, and molecular docking simulation studies. Some of the compounds behaved differently in case ofBacillus pasteuriiurease. We conducted the enzyme kinetics, UV-visible spectroscopy, and molecular docking results in terms of the known protein structure of the enzyme. We also evaluated possible molecular interpretations for the site of biscoumarins binding and found that phenyl ring is the major active pharmacophore. The excellent in vitro potency and selectivity profile of the several compounds described combined with their nontoxicity against the human cells and plants suggest that these compounds may represent a viable lead series for the treatment of urease associated problems.

Natural products, longissiminone A (1) and longissiminone B (2), were isolated along with a known compound, glutinol (3), from a medicinal lichen, Usnea longissima. The structures of compounds 1 and 2 were determined with the help of spectroscopic studies. Compound 1 was found to possess potent anti-inflammatory activity in a cell-based contemporary assay. Cytotoxicity activity measured by cell viability assay showed 100% viability in the presence of 200 microg/mL conc. of these compounds.

—Nine new cassane-type diterpenes, named taepeenin A–I, and two new norcassane-type diterpenes, named nortaepeenin A–B,were isolated from the stems and roots of Caesalpinia crista along with three known diterpenes: vinhaticoic acid, methyl vinhaticoate andent-11b-hydroxy-rosa-5,15-diene. Their structures were elucidated on the basis of spectroscopic analysis. In addition, the structure oftaepeenin A was confirmed by X-ray diffraction analysis.q 2005 Elsevier Ltd. All rights reserved. 1. IntroductionCassane-type diterpenoids are characteristic components ofthe genus Caesalpinia of the Leguminosae family. One ofthem, the plant Caesalpinia crista L., known locally as‘Taepee’ in Thai, is a climber distributed from India andCeylon through most of Southeast Asia to the Ryu-KyuIslands, Queensland, and Caledonia. 1 The leaves, roots, andfruits of this plant are used as a tonic and an antiperiodic. 2 The seed kernels of C. crista displayed interestingantimalarial activity. 3 Previous chemical investigations ofthe seed kernels have revealed the presence of severalcassane-type diterpenoids.

Phytochemical investigations on the organic extracts of the leaves of Suregada multiflora have led to the isolation of ten tetracyclic diterpene lactones 1–10 , members of a rare class of abiatene diterpene lactones. Compounds 1–5 were found to be new. The structures of gelomulides F ( 11 ), D ( 12 ) and E ( 13 ) were revised on the basis of 2D NMR and X-ray diffraction evidences. Compounds 1 and 2 contain an epoxy linkage between C-8 and C-14, whereas compounds 3–5 were identified as 8,14-dihydroxy analogues of diterpene lactones. The stereochemical assignments in new compound 1 are based on X-ray diffraction analysis. Compounds 6 and 7 were identified as the known gelomulides A , G . The structures of compounds 7–9 were unambiguously confirmed by X-ray diffraction analyses.

Phytochemical investigation on Cocculus pendulus (J. R. & G. FORST.) resulted in the isolation of two new and three known bisbenzylisoquinoline alkaloids. The structures of the new alkaloids, kurramine-2'-beta-N-oxide (1) and kurramine-2'-alpha-N-oxide (2), were elucidated with the help of spectroscopic techniques. The cholinesterase inhibitory activities of these bisbenzylisoquinoline alkaloids are reported here for the first time.

Here, we explore the mechanism of action of isoxylitone (ISOX), a molecule discovered in the plant Delphinium denudatum, which has been shown to have anticonvulsant properties. Patch-clamp electrophysiology assayed the activity of ISOX on voltage-gated sodium channels (VGSCs) in both cultured neurons and brain slices isolated from controls and rats with experimental epilepsy(kindling model). Quantitative transcription polymerase chain reaction (qRT-PCR) (QPCR) assessed brain-derived neurotrophic factor (BDNF) mRNA expression in kindled rats, and kindled rats treated with ISOX. ISOX suppressed sodium current (I(Na)) showing an IC50 value of 185 nM in cultured neurons. ISOX significantly slowed the recovery from inactivation (ISOX τ = 18.7 ms; Control τ = 9.4 ms; p < 0.001). ISOX also enhanced the development of inactivation by shifting the Boltzmann curve to more hyperpolarized potentials by -11.2 mV (p < 0.05). In naive and electrically kindled cortical neurons, the IC50 for sodium current block was identical to that found in cultured neurons. ISOX prevented kindled stage 5 seizures and decreased the enhanced BDNF mRNA expression that is normally associated with kindling (p < 0.05). Overall, our data show that ISOX is a potent inhibitor of VGSCs that stabilizes steady-state inactivation while slowing recovery and enhancing inactivation development. Like many other sodium channel blocker anti-epileptic drugs, the suppression of BDNF mRNA expression that usually occurs with kindling is likely a secondary outcome that nevertheless would suppress epileptogenesis. These data show a new class of anti-seizure compound that inhibits sodium channel function and prevents the development of epileptic seizures.

Structural transformation of the sesquiterpene ester, ferutinin (1), by suspended fungal cultures of Aspergillus niger, Rhizopus stolonifer, and Fusarium lini, resulted in the formation of a metabolite. This metabolite was identified as ferutinin α-epoxide (2), by different spectroscopic techniques. Metabolite 2 showed a good antibacterial activity against Staphylococcus aureuscompared to ferutinin (1).

The fungal transformation of cedryl acetate ( 1) was investigated for the first time by using Cunninghamella elegans . The metabolites obtained include, 10β-hydroxycedryl acetate ( 3 ), 2α, 10β-dihydroxycedryl acetate ( 4 ), 2α-hydroxy-10-oxocedryl acetate ( 5 ), 3α,10β-dihydroxycedryl acetate ( 6 ), 3α,10α-dihydroxycedryl acetate ( 7 ), 10β,14α-dihydroxy cedryl acetate ( 8 ), 3β,10β-cedr-8(15)-ene-3,10-diol ( 9 ), and 3α,8β,10β -dihydroxycedrol ( 10 ). Compounds 1 , 2 , and 4 showed α-glucosidase inhibitory activity, whereby 1 was more potent than the standard inhibitor, acarbose, against yeast α-glucosidase. Detailed docking studies were performed on all experimentally active compounds to study the molecular interaction and binding mode in the active site of the modeled yeast α-glucosidase and human intestinal maltase glucoamylase. All active ligands were found to have greater binding affinity with the yeast α-glucosidase as compared to that of human homolog, the intestinal maltase, by an average value of approximately −1.4 kcal/mol, however, no significant difference was observed in the case of pancreatic amylase.

Salvialeriol ( 1 ), a new abietane-type diterpene, was isolated from Salvia leriifolia Benth. ( Salvia leriaefolia ), along with two known abietane-type diterpenoids, 6-hydroxysalvinolone ( 2 ) and deacetylnemorone ( 3 ), and two known triterpenes, 2-acetoxylupeol ( 4 ), and lupine-2,3-diol ( 5 ). Compounds 2–5 are reported here for the first time from this species. Compound 4 was previously reported as a synthetic derivative of 5 and this is the first report of its isolation from a natural source. Compounds 2 , 3 and 5 exhibited a potent antiproliferative activity against the prostate cancer cell lines (PC3) with IC 50 of 3.9 ± 0.1, 6.2 ± 0.1 and 2.8 ± 0.1 μM, respectively, and cervical cancer cell lines (HeLa) with IC 50 of 8.0 ± 0.3, 2.6 ± 0.1 and 2.7 ± 0.1 μM, respectively. Whereas compounds 1 and 4 showed moderate antiproliferative activities against the cell lines. Compounds 1 – 5 were also evaluated for the inhibition of α-chymotrypsin, a protease enzyme, and 2 exhibited a competitive inhibition of the enzyme (IC 50 = 188.8 μM).

From the leaves of Sarcococca coriacea two new steroidal alkaloids, epoxynepapakistamine-A [(20S)-20-(N-methylamino)-3beta-(tigloylamino)-5alpha-pregna-16alpha,17alpha-epoxy-2beta,4beta-di-O-acetate] (1), and epoxysarcovagenine-D [(20S)-20-(N-methylamino)-3beta-(tigloylamino)-5alpha-pregna-2-en-16alpha,17alpha-epoxy-4-one] (2), and two known compounds funtumafrine C [(20S)-20-(N,N-dimethylamino)-5alpha-pregna-3-one] (3) and N-methylfuntumine (4) were isolated. Their structures were elucidated on the basis of their spectral properties. The compounds 1, 3 and 4 were found to have cholinesterase inhibitory activity when tested for the inhibition of electric eel acetylcholinesterase and horse serum butyrylcholinesterase. They inhibited both enzymes in a concentration dependent fashion.

Microbial transformation of methasterone (1) was investigated with Macrophomina phaseolina, Cunninghamella blakesleeana, and Fusarium lini. Biotransformation of 1 with M. phaseolina yielded metabolite 2, while metabolites 3-7 were obtained from the incubation of 1 with C. blakesleeana. Metabolites 8-13 were obtained through biotransformation with F. lini. All metabolites, except 13, were found to be new. Methasterone (1) and its metabolites 2-6, 9, 10, and 13 were then evaluated for their immunomodulatory effects against TNF-α, NO, and ROS production. Among all tested compounds, metabolite 6 showed a potent inhibition of proinflammatory cytokine TNF-α (IC50=8.1±0.9μg/mL), as compared to pentoxifylline used as a standard (IC50=94.8±2.1μg/mL). All metabolites were also evaluated for the inhibition of NO production at concentration of 25μg/mL. Metabolites 6 (86.7±2.3%) and 13 (62.5±1.5%) were found to be the most potent inhibitors of NO as compared to the standard NG-monomethyl-l-arginine acetate (65.6±1.1%). All metabolites were found to be non-toxic against PC3, HeLa, and 3T3 cell lines. Observed inhibitory potential of metabolites 6 and 13 against pro-inflammatory cytokine TNF-α, as well as NO production makes them interesting leads for further studies.

Seven metabolites were obtained from the microbial transformation of anabolic-androgenic steroid mibolerone (1) with Cunninghamella blakesleeana, C. echinulata, and Macrophomina phaseolina. Their structures were determined as 10β,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (2), 6β,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (3), 6β,10β,17β-trihydroxy-7α,17α-dimethylestr-4-en-3-one (4), 11β,17β-dihydroxy-(20-hydroxymethyl)-7α,17α-dimethylestr-4-en-3-one (5), 1α,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (6), 1α,11β,17β-trihydroxy-7α,17α-dimethylestr-4-en-3-one (7), and 11β,17β-dihydroxy-7α,17α-dimethylestr-4-en-3-one (8), on the basis of spectroscopic studies. All metabolites, except 8, were identified as new compounds. This study indicates that C. blakesleeana, and C. echinulata are able to catalyze hydroxylation at allylic positions, while M. phaseolina can catalyze hydroxylation of CH2 and CH3 groups of substrate 1. Mibolerone (1) was found to be a moderate inhibitor of β-glucuronidase enzyme (IC50 = 42.98 ± 1.24 μM) during random biological screening, while its metabolites 2-4, and 8 were found to be inactive. Mibolerone (1) was also found to be significantly active against Leishmania major promastigotes (IC50 = 29.64 ± 0.88 μM). Its transformed products 3 (IC50 = 79.09 ± 0.06 μM), and 8 (IC50 = 70.09 ± 0.05 μM) showed a weak leishmanicidal activity, while 2 and 4 were found to be inactive. In addition, substrate 1 (IC50 = 35.7 ± 4.46 μM), and its metabolite 8 (IC50 = 34.16 ± 5.3 μM) exhibited potent cytotoxicity against HeLa cancer cell line (human cervical carcinoma). Metabolite 2 (IC50 = 46.5 ± 5.4 μM) also showed a significant cytotoxicity, while 3 (IC50 = 107.8 ± 4.0 μM) and 4 (IC50 = 152.5 ± 2.15 μM) showed weak cytotoxicity against HeLa cancer cell line. Compound 1 (IC50 = 46.3 ± 11.7 μM), and its transformed products 2 (IC50 = 43.3 ± 7.7 μM), 3 (IC50 = 65.6 ± 2.5 μM), and 4 (IC50 = 89.4 ± 2.7 μM) were also found to be moderately toxic to 3T3 cell line (mouse fibroblast). Interestingly, metabolite 8 showed no cytotoxicity against 3T3 cell line. Compounds 1-4, and 8 were also evaluated for inhibition of tyrosinase, carbonic anhydrase, and α-glucosidase enzymes, and all were found to be inactive.

A new adduct of abietane-type diterpene, salvialeriicone (1), was isolated from Salvia leriifolia Benth., along with a new chemical entity nor-abietane diterpene, 2-isopropyl-8,8-dimethyl-7,8-dihydrophenanthrene-1,4,5(6H)-trione (2). Their structures were determined using mass spectrometry, and 1D- and 2D-NMR spectroscopy. Salvialeriicone: A new compound from Salvia leriifolia Benth.

Tyramine derivatives 3-27 were synthesized by using conventional and environmental friendly ultrasonic techniques. These derivatives were then evaluated for the first time for their α-glucosidase (Sources: Saccharomyces cerevisiae and mammalian rat-intestinal acetone powder) inhibitory activity by using in vitro mechanism-based biochemical assays. Compounds 7, 14, 20, 21 and 26 were found to be more active (IC50 = 49.7 ± 0.4, 318.8 ± 3.7, 23.5 ± 0.9, 302.0 ± 7.3 and 230.7 ± 4.0 μM, respectively) than the standard drug, acarbose (IC50 = 840.0 ± 1.73 μM (observed) and 780 ± 0.028 μM (reported)) against α-glucosidase obtained from Saccharomyces cerevisiae. Kinetic studies were carried out on the most active members of the series in order to determine their mode of inhibition and dissociation constants. Compounds 7, 20 and 26 were found to be the competitive inhibitors of α-glucosidase. These compounds were also screened for their protein antiglycation, and dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. Only compounds 20, 22 and 27 showed weak antiglycation activity with IC50 values 505.27 ± 5.95, 581.87 ± 5.50 and 440.58 ± 2.74 μM, respectively. All the compounds were found to be inactive against DDP-IV enzyme. Inhibition of α-glucosidase, DPP-IV enzymes and glycation of proteins are valid targets for the discovery of antidiabetic drugs. Cytotoxicity of compounds 3-27 was also evaluated by using mouse fibroblast 3T3 cell lines. All the compounds were found to be noncytotoxic. The current study describes the synthesis α-glucosidase inhibitory activity of derivatives, based on a natural product tyramine template. The compounds reported here may serve as the starting point for the design and development of novel α-glucosidase inhibitors as antidiabetic agents.