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Fungal transformation of methasterone resulted in six products (2–7). 2–5, and 7 were identified as new. Substrate 1 showed remarkable anti-inflammatory activity but was cytotoxic. Products 2 and 7 showed moderate activity but were non-cytotoxic.

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).

Primary objective of the study was to assess health-related quality of life and associated factors (gender, age, education, income, marital status and expenses) that affect quality of life among senior citizens in Islamabad, Pakistan. A community-based cross-sectional study was designed to assess the health-related quality of life among senior citizens in the territory of Islamabad, Pakistan. Convenient sampling technique was used to collect the data from 385 participants. A pre-validated tool SF-36 was used to collect the data. Data was clean coded and analyzed by SPSS. The overall health-related quality of life score (55.79) was poor. Females had less quality-of-life score (50.84) as compared to males (59.74). Uneducated had a poor score (46.54) than educated (64.70). Age group (60-70 years) had a good quality of life score (60.07) as compared to the elder age groups (47.16). Married participants had a better quality of life score (57.67) than unmarried, divorced and widowed participants (53.58, 46.85, and 47.39 respectively). Participants with low monthly income showed low quality of life score (46.99) which was increased to (63.95) with an increment in monthly income. Participants who were financially independent had a better health-related quality of life score (59.44) as compared to those who were dependent on family (53.05) or government annuity (41.16). These findings suggested the requirement for effective health promotion strategies to improve overall health status among the elderly. The health systems needed to be aligned to meet the needs of older people. Retirement age should be extended to 65 year of age.

Several androgenic steroids have been biotransformed by fungi into metabolites with numerous biological properties. Incubation of norandrostenedione (1) with Fusarium lini NRRL 2204 was carried out for the first time, yielding two new metabolites, 3,7β-dihydroxy-19-norandrost-1,3,5-trien-17-one (3) and 6α,10β,17β-trihydroxy-19-nor-4-androsten-3-one (4), along with three known compounds, 3-hydroxy-19-norandrost-1,3,5-trien-17-one (2), 10β, 17β-dihydroxy-19-nor-4-androsten-3-one (5) and 10β-hydroxy-19-nor-4- androsten-3,17-dione (6). Their structures were elucidated by extensive spectroscopic analyses, including 1D-, 2D-NMR, and HR-MS experiments. Substrate 1 and its derivatives 2-6 were evaluated in vitro for their urease and chymotrypsin inhibitory properties. Compounds 2 and 3 were found to have strong urease activity with IC50 = 23.7 ± 0.17 and 10.2 ± 0.28 μm, respectively, as compared to the standard drug thiourea (IC50 = 21.6 ± 0.12 μm). Compounds 4, 5 and 6 showed good chymotrypsin activity with IC50 values of 6.4 ± 0.19, 15.6 ± 0.46 and 18.4 ± 0.65 μm, respectively, as compared to standard chymostatin with IC50 = 5.7 ± 0.14 μm. These transformed metabolites may form the basis for the future development of new drugs against ulcer, inflammation, bacterial and viral diseases.

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.

A synthetic anabolic-androgenic steroid, methylstenbolone (1), was structurally transformed into a series of nine analogues, 2,17α-dimethyl-7α,17β-dihydroxy-5α-androst-1-en-3-one (2), 2,17α-dimethyl-15β,17β-dihydroxy-5α-androst-1-en-3-one (3), 2,17α-dimethyl-6α,9α,17β-trihydroxy-5α-androst-1-en-3-one (4), 2-methyl-17β-hydroxy-17α-(hydroxymethyl)-5α-androst-1-en-3-one (5), 2-methyl-11β,17β-dihydroxy-17α-(hydroxymethyl)-5α-androst-1-en-3-one (6), 2-methyl-17β-hydroxy-17α-(hydroxymethyl)-5α-androst-1-en-3,6-dione (7), 2-methyl-17β-hydroxy-17α-(hydroxymethyl)-5β-androst-1-en-3,6-dione (8), 2,17α-dimethyl-7β,17β-dihydroxy-5α-androst-1-en-3-one (9), and 2,17α-dimethyl-12β,17β-hydroxy-5α-androst-1-en-3,7-dione (10) by fungal cell suspension cultures, Macrophomina phaseolina and Cunninghamella blakesleeana for the first time. Among those, compounds 2-4 and 6-10 were identified as new. Herein, spectral data of metabolite 5 was reported for the first time. Their structures were elucidated by NMR, MS, UV, and IR spectroscopic methods. Substrate 1 (ICsub50/sub10.1 ± 0.3 µg/mL) was identified as a potent anti-inflammatory agent against nitric oxide (NO) production. Its transformed products 3 (ICsub50/subas 27.8 ± 1.1 µg/mL) and 9 (26.9 ± 0.4 µg/mL) displayed good inhibition. Compounds 2 (ICsub50/sub = 45.9 ± 0.8 µg/mL) and 6 (ICsub50/sub = 36.6 ± 1.2 µg/mL) were also active moderately against NO production, in comparison to standard LNMMA (ICsub50/sub = 24.2 ± 0.8 µg/mL). Cytotoxicity assay showed 1 was active to cancer cell line MCF7 (ICsub50/sub = 12.26 ± 0.35 µg/mL), compared to the standard Doxorubicin having ICsub50/subas 1.25 ± 0.11 µg/mL. However, it is also toxic to human normal cell line (BJ) with ICsub50/subas 8.69 ± 0.02 µg/mL. More importantly, all transformed products are non-cytotoxic on BJ. Therefore, biotransformation can be an efficient approach to reduce the toxicity of methylstenbolone.

Natural mucilages are auspicious biodegradable polymeric materials. The aim of the present research work was to elucidate the characteristics of quince mucilage-based polymeric network for sustained delivery of metprolol tartrate and its toxicity evaluation. Mucilage was extracted by hot water extraction, and characterization of quince mucilage was accomplished by using Fourier transform infrared (FTIR) spectroscopy. Different batches of quince mucilage polymeric network were prepared by free radical polymerization by utilizing varying ratios of quince mucilage, acrylamide and crosslinker. Degree of swelling depends on concentration of mucilage, monomer and also on crosslinking density of polymeric network. FTIR illustrates proficient grafting, and morphological (scanning electron microscopy) analysis signified porous design. Hence, quince mucilage-based design was encouraging for sustained delivery of metprolol tartrate and acute toxicity evaluation proved that mucilage-based network was safe for oral drug delivery system.

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.

Cunninghamella blakesleeana-mediated biotransformation of an oral contraceptive drug, levonorgestrel (1), yielded a new metabolite, 13β-ethyl-17α-ethynyl-10,17β-dihydroxy-4,6-dien-3-one (2), and two known metabolites 3 (13β-ethyl-17α-ethynyl-10β,17β-dihydroxy-4-en-3-one), and 4 (13β-ethyl-17α-ethynyl-6β,17β-dihydroxy-4-en-3-one) at an ambient temperature using aqueous media. Hydroxylation and dehydrogenation of compound 1 was observed during the bio-catalytic transformation. The structure of a new metabolite 2 was determined by 1H, 13C, and 2DNMR and HR-EIMS spectroscopic techniques.

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.

Although the discovery of antibiotics has decreased the spread and severity of infectious diseases, their uncontrolled use has lead to the emergence of bacterial resistance to existing chemotherapeutic agents. Bacterial disease thus remains a challenge for health authorities in worldwide and especially in sub-Saharan Africa. Despite their efficacy, the miss-use of medicinal plants for the treatment of infectious diseases couple to the farming and hunting activities has contribute enormously to the destruction of many medicinal plant species. In search of an alternative for new and effective agents against bacterial infection, norandrostenedion (19-nor-4-androsten-3,17-dione) (1), was biotransformed by Cunninghamella blakesleeana ATCC 8688A and yielded a new metabolite, 6α,10 β -dihydroxy-19-nor-4-androsten-3-one (2), together with three known compounds, 10 β -hydroxy-19-nor-4-androsten-3,17-dione (3), 6 β,10 β,17 β -trihydroxy-19-nor-4-androsten-3-one (4) and 10 β,17 β -dihydroxy-19-nor-4-androsten-3-one (5). Their structures were elucidated on the basis ofspectroscopic techniques: NMR analysis (1D and 2D) and HRIE-MS and by comparison with previously reported data. In addition, the agar diffusion method was used to evaluate the diameter of the inhibition zone and INT colorimetric assay for MIC values. All metabolites obtained showed a potent and varied activity against tested bacteria. These results support the uses of biotransformation to develop new antimicrobial compounds for clinical application.

Biotransformation of an orally active contraceptive drug, desogestrel (1), with Cunninghamella elegans yielded a new metabolite, 13β-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-17β-ol-3,6-dione (2), along with five known metabolites, i.e., 13β-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-3β,6β,17β-triol (3), 13β-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-6β,17β-diol-3-one (4), 13β-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-17β-ol-3-one (5), 13β-ethyl-11-epoxy-18,19-dinor-17α-pregn-4-en-20-yn-17β-ol-3-one (6), and 13β-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-10β,17β-diol-3-one (7). The structure of new metabolite 2 was elucidated by using 1H-, 13C-, and 2D-NMR, EI-, and HREI-MS, IR, and UV spectroscopic data. Compounds 1–7 were evaluated for anti-inflammatory activities, i.e., inhibition of T-cell proliferation, and pro-inflammatory cytokine (TNF-α). Compounds 1 (IC50 = 1.12 ± 0.03 µg/mL), 2 (IC50 = 1.15 ± 0.05 µg/mL), 3 (IC50 = 1.15 ± 0.05 µg/mL), 4 (IC50 = 1.40 ± 0.03 µg/mL), 5 (IC50 = 1.78 ± 0.08 µg/mL), and 6 (IC50 = 1.36 ± 0.07 µg/mL) were identified as potent inhibitors of T-cells proliferation, in comparison to the standard drug, prednisolone (IC50 = 3.51 ± 0.03 µg/mL). Compound 7 (IC50 = 6.18 ± 0.04 µg/mL) showed a good activity. In addition, substrate 1 (IC50 ≤ 1 µg/mL), and its metabolites 2 (IC50 = 4.1 ± 0.60 µg/mL), and 6 (IC50 = 6.8 ± 0.8 µg/mL) also showed a potent inhibition of pro-inflammatory cytokine (TNF-α) production, as compared to the standards drug, pentoxifilline (IC50 = 94.8 ± 2.1 µg/mL). Whereas compounds 3 (IC50 = 57.9 ± 7.6 µg/mL), and 5 (IC50 = 27.2 ± 6.8 µg/mL) showed a moderate inhibition of TNF-α production, while compounds 4 and 7 showed no inhibition. Compounds 1–7 were found to be non-cytotoxic to 3T3 normal cell line (mouse fibroblast).

International audience; Staphylococcus aureus is one of the most infectious agents among staphylococcal bacteria. Currently many strains of S. aureus have developed resistance against available antibiotics. Therefore, the treatment of infections caused by them is a major challenge. During current study, desogestrel (1), a contraceptive drug, was found to be a potent growth inhibitor of drug resistant strains of S. aureus. Therefore, in search of new and effective agents against multi-drug resistant S. aureus strains, whole-cell bio-catalytic conversion of desogestrel (1) by Cunninghamella blakesleeana ATCC 8688A at pH 7.0 and 25 °C was carried out, yielding three new metabolites, 13-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-6β,15β,17β-triol (2), 13-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-3β,6β,17β-triol (3), and 13-ethyl-11-methylene-18,19-dinor-17α-pregn-20-yn-3α,5α,6β,17β-tetraol (4), along with a known metabolite, 13-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-6β,17β-dihydroxy-3-one (5). Among them, compounds 1–2 showed a potent activity against S. aureus EMRSA-17, S. aureus NCTC 13277 (MRSA-252), and S. aureus NCTC 13143, and clinically isolated Pakistani strain of S. aureus in an in vitro Microplate Alamar Blue Assay (MABA). Vancomycin was used as the standard drug in this assay. In addition, compound 1 also showed a significant activity against vancomycin-resistant S. aureus (VRSA) ATCC 700699. Compounds 1–5 were also evaluated against 3T3 normal cell line (mouse fibroblast) where they all were identified as non-cytotoxic. The present study thus provides new leads for the development of anti-bacterial drugs against MDR S. aureus.

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.