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Publikationen - Natur- und Wirkstoffchemie

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Bücher und Buchkapitel

Hussain, H.; Elizbit, .; Ali, I.; Mamadalieva, N. Z.; Abbas, G.; Ali, M.; Zaman, G.; Khan, A.; Hassan, U.; Green, I. R.; Fruitful decade of Phoma secondary metabolites from 2011 to 2020: Chemistry, chemical diversity, and biological activities (Rai, M., Zimowska, B., Kövics, G.J.). Phoma: Diversity, Taxonomy, Bioactivities, and Nanotechnology 183–203, (2022) ISBN: 978-3-030-81217-1 DOI: 10.1007/978-3-030-81218-8_10

Fungi have been an extraordinary area of scientific research, and many secondary metabolites with intriguing chemical diversity along with interesting biological activities have been identified. Fungi like Phoma sp. have been investigated as a source of structurally unique metabolites over the past 10 years (2011–2020). A diverse range of natural products, viz., α-pyrone derivatives, isocoumarins, anthraquinones, xanthones, thiodiketopiperazines, cytochalasin derivatives, diphenyl ether derivatives, furopyrans, xyloketals, chromones, meroterpenoids, diterpenoids, polyketides, and alkaloids, have been reported from various Phoma spp. These metabolites illustrated phytotoxic, cytotoxic, antibacterial, antifungal, herbicidal, immunosuppressive, antiviral, antidiabetic (PTP1B inhibition), anti-Alzheimer (acetylcholinesterase inhibition), and antioxidant activities.
Publikation

Nazir, M.; Saleem, M.; Ali, I.; Abbas, G.; Rehman, N. U.; Green, I. R.; Hussain, W.; Khan, S.; Hussain, H.; Fungal metabolites as anti-diabetic agents: emphasison PTP1B inhibitors Phytochemistry 20, 119-143, (2021) DOI: 10.1007/s11101-020-09701-9

In the last decade the prevalence of diabetes has escalated globally and it is estimated that the number of diabetic people will increase to 642 million by 2040. Although numerous classes of pharmaceutical drugs are available to treat Type ll diabetes, they manifest certain side effects. PTP1B has attracted significant interest as an important therapeutic agent and has been validated to target diabetes and obesity. Fungi, in general, produce secondary metabolites with some amazing chemical and structural diversity and are recognized to be a valuable source for therapeutic molecules. In this review, the focus is on describing the PTP1B effects and their potential as anti-diabetic agents for the various metabolites isolated from fungi.
Publikation

Ur Rehman, N.; Halim, S. A.; Khan, M.; Hussain, H.; Yar Khan, H.; Khan, A.; Abbas, G.; Rafiq, K.; Al-Harrasi, A.; Antiproliferative and Carbonic Anhydrase II Inhibitory Potential of Chemical Constituents from Lycium shawii and Aloe vera: Evidence from In Silico Target Fishing and In Vitro Testing Pharmaceuticals 13, 94, (2020) DOI: 10.3390/ph13050094

Lycium shawii Roem. & Schult and resin of Aloe vera (L.) BURM. F. are commonly used in Omani traditional medication against various ailments. Herein, their antiproliferative and antioxidant potential was explored. Bioassay-guided fractionation of the methanol extract of both plants led to the isolation of 14 known compounds, viz., 1–9 from L. shawii and 10–20 from A. vera. Their structures were confirmed by combined spectroscopic techniques including 1D (1H and 13C) and 2D (HMBC, HSQC, COSY) nuclear magnetic resonance (NMR), and electrospray ionization-mass spectrometry (ESI-MS). The cytotoxic potential of isolates was tested against the triple-negative breast cancer cell line (MDA-MB-231). Compound 5 exhibited excellent antiproliferative activity in a range of 31 μM, followed by compounds 1–3, 7, and 12, which depicted IC50 values in the range of 35–60 μM, while 8, 6, and 9 also demonstrated IC50 values >72 μM. Subsequently, in silico target fishing was applied to predict the most potential cellular drug targets of the active compounds, using pharmacophore modeling and inverse molecular docking approach. The extensive in silico analysis suggests that our compounds may target carbonic anhydrase II (CA-II) to exert their anticancer activities. When tested on CA-II, compounds 5 (IC50 = 14.4 µM), 12 (IC50 = 23.3), and 2 (IC50 = 24.4 µM) showed excellent biological activities in vitro. Additionally, the ethyl acetate fraction of both plants showed promising antioxidant activity. Among the isolated compounds, 4 possesses the highest antioxidant (55 μM) activity followed by 14 (241 μM). The results indicated that compound 4 can be a promising candidate for antioxidant drugs, while compound 5 is a potential candidate for anticancer drugs.
Publikation

Ur Rehman, N.; Hussain, H.; Khan, H. Y.; Abbas, G.; Hidayatullah, .; Al-Harrasi, A.; A New Anticancer Bisflavan-3-Ol from Boerhavia elegans Chem. Nat. Compd. 56, 235-238, (2020) DOI: 10.1007/s10600-020-02995-3

A new a bisflavan-3-ol, boerhavianane (1), was isolated from Boerhavia elegans L. The structure of the flavanol dimer was elucidated by detailed spectroscopic analysis including 1H, 13C NMR, COSY, HMQC, HMBC, and ESI-MS. Boerhavianane (1) was evaluated for its anticancer activity and demonstrated a significant reduction in the viability of breast cancer cells in a concentration-dependent manner with an IC50 value of 38.48 μg/mL. Moreover, boerhavianane (1) was also screened for DPPH antioxidant activity and acetyl cholinesterase, xanthine oxidase, urease, and α-glucosidase enzyme inhibition activities. Preliminary results showed that it exhibited significant inhibition (81.0 ± 2.0%) against urease enzyme, whereas for DPPH radical scavenging it showed moderate activity (75.0 ± 1.5%).
Publikation

Hussain, H.; Ali, I.; Wang, D.; Mamadalieva, N. Z.; Hussain, W.; Csuk, R.; Loesche, A.; Fischer, L.; Staerk, D.; Anam, S.; AlZain, M. N.; Mushtaq, M.; Ul-Haq, Z.; Ullah, R.; Noman, O. M.; Abbas, G.; Green, I. R.; 4-Benzyloxylonchocarpin and Muracatanes A-C from Ranunculus muricatus L. and Their Biological Effects Biomolecules 10, 1562, (2020) DOI: 10.3390/biom10111562

Ranunculus muricatus L. is a spiny fruit buttercup that is used in various traditional medicinal systems. In the current investigation of R. muricatus, the new chalcone 4-benzyloxylonchocarpin (1), the new anthraquinone muracatanes A (2), the new-to-nature anthraquinone muracatanes B (3), and the new naphthalene analog muracatanes C (4) were isolated, in addition to the three previously reported compounds, 4-methoxylonchocarpin (5), β-sitosterol (6), and β-sitosterol β-D-glucopyranoside (7). Their structures were elucidated using 1D (1H and 13C) and 2D (COSY, HSQC, and HMBC) NMR spectroscopy and HR-ESI-MS. Chalcone 1 showed potent acetylcholinesterase inhibitory effects with Ki of 5.39 µM and Ki′ of 3.54 µM, but none of the isolated compounds showed inhibitory activity towards butyrylcholinesterase. Anthraquinone 3 illustrated α-glucosidase inhibitory effects with IC50-values of 164.46 ± 83.04 µM. Compound 5 displayed moderate cytotoxic activity towards ovarian carcinoma (A2780, IC50 = 25.4 µM), colorectal adenocarcinoma (HT29, IC50 = 20.2 µM), breast cancer (MCF7, IC50 = 23.7 µM), and thyroid carcinoma (SW1736, IC50 = 26.2 µM) while it was inactive towards pharynx carcinoma (FaDu: IC50 > 30 µM).
Publikation

Abbas, G.; Haq, Q. M. I.; Hamaed, A.; Al-Sibani, M.; Hussain, H.; Glucagon and Glucagon-like Peptide-1 Receptors: Promising Therapeutic Targets for an Effective Management of Diabetes Mellitus Curr. Pharm. Des. 26, 501-508, (2020) DOI: 10.2174/1381612826666200131143231

G-protein-coupled receptors (GPCRs) are membrane-bound proteins which are responsible for the detection of extracellular stimuli and the origination of intracellular responses. Both glucagon and glucagon-like peptide-1 (GLP-1) receptors belong to G protein-coupled receptor (GPCR) superfamily. Along with insulin, glucagon and GLP-1 are critical hormones for maintaining normal serum glucose within human body. Glucagon generally plays its role in the liver through cyclic adenosine monophosphate (cAMP), where it compensates the action of insulin. GLP-1 is secreted by the L-cells of the small intestine to stimulate insulin secretion and inhibit glucagon action. Despite the extensive research efforts and the multiple approaches adopted, the glycemic control in the case of type-2 diabetes mellitus remains a major challenge. Therefore, a deep understanding of the structure-function relationship of these receptors will have great implications on future therapies in order to maintain a normal glucose level for an extended period of time. The antagonists of glucagon receptor that can effectively block the hepatic glucose production, as a result of glucagon action, are highly desirable for the tuning of the hyperglycemic state in type 2 diabetes mellitus. In the same manner, GLP-1R agonists act as important treatment modalities thanks to their multiple anti-diabetic actions to attain normal glucose level. In this review article, the structural diversity of glucagon and GLP-1 receptors along with their signaling pathways, site-directed mutations and significance in drug discovery against type-2 diabetes will be illustrated. Moreover, the promising non-peptide antagonists of glucagon receptor and agonists of GLP-1 receptor, for the management of diabetes will be presented with elaboration on the structure-activity relationship (SAR).
Bücher und Buchkapitel

Abbas, G.; Ali, M.; Hamaed, A.; Al-Sibani, M.; Hussain, H.; Al-Harrasi, A.; Azadirachta indica: the medicinal properties of the global problems-solving tree (Ozturk, M. et al., eds.). 305-316, (2020) ISBN: 9780128223703 DOI: 10.1016/B978-0-12-819541-3.00017-7

The Azadirachta indica, which is commonly known as the neem tree, has gained prominence thanks to its wide spectrum of medicinal properties and its great potential to treat various diseases. In 1992 the US National Academy of Sciences recognized the importance of this plant and declared neem as a tree for solving global problems. The A. indica belongs to the family Meliaceae. It is a fast growing tropical evergreen tree indigenous to the Indo-Pakistan subcontinent since antiquity. The A. indica is also known as a wonder tree due to its richness in bioactive components in all parts of the tree such as the leaves, the bark, the flowers, the fruits, the seeds, the roots, and the gum oil and therefore it is highly exploitable. Over the years, a large number of diverse types of chemical constituents belonging to the various classes of compounds such as flavonoids, alkaloids, triterpenoids, steroids, carotenoids, and ketones, as well as phenolic compounds, have been extracted from the neem plant. The ultimate goal is to promote plant-derived products with the least side effects as modern drugs. In the last few decades, apart from the chemical analysis of the neem compounds, many researchers have investigated the potential of natural products as candidate medications for the treatment of various diseases. As a summary, substantial progress has been made in identifying neem-derived bioactive compounds for the development of medications for the treatment of a wide range of diseases. In this chapter, the major bioactive components of A. indica are presented along with their applications for the cure of many life-threatening diseases.
Publikation

Shamraiz, U.; Ahmad, Z.; Badshah, A.; Hussain, H.; Abbas, G.; Ullah, S.; Raza, B.; α-glucosidase inhibition (antidiabetic) of rubidium doped indium sulfide nanomaterials Mater. Res. Express 6, 115051, (2019) DOI: 10.1088/2053-1591/ab4766

Herein, we report the In2S3 and rubidium doped In2S3 (Rb- In2S3) nanostructures and elucidate their role in α-glucosidase inhibition (AIGs). The phase, crystal structure, morphology, and composition of the as prepared In2S3 and Rb- In2S3 nanostructures was characterized by PXRD, SEM, TEM and EDS analysis, respectively. Pure In2S3 were unable to impart significance glucosidase inhibition activity, while the activity was remarkably enhanced with the doping of 5% Rb. The mass percentage of Rb (0.42 μg ml−1) is much lower than the transition metals-based drugs reported in the literature.
Publikation

Hussain, H.; Green, I. R.; Abbas, G.; Adekenov, S. M.; Hussain, W.; Ali, I.; Protein tyrosine phosphatase 1B (PTP1B) inhibitors as potential anti-diabetes agents: patent review (2015-2018) Expert Opin. Ther. Pat. 29, 689-702, (2019) DOI: 10.1080/13543776.2019.1655542

Introduction: Protein tyrosine phosphatase 1B (PTP1B) inhibition has been recommended as a crucial strategy to enhance insulin sensitivity in various cells and this fact is supported by human genetic data. PTP1B inhibitors improve the sensitivity of the insulin receptor and have the ability to cure insulin resistance-related diseases. In the latter years, targeting PTP1B inhibitors is being considered an attractive target to treat T2DM and therefore libraries of PTP1B inhibitors are being suggested as potent antidiabetic drugs.Areas covered: This review provides an overview of published patents from January 2015 to December 2018. The review describes the effectiveness of potent PTP1B inhibitors as pharmaceutical agents to treat type 2 diabetes.Expert opinion: Enormous developments have been made in PTP1B drug discovery which describes progress in natural products, synthetic heterocyclic scaffolds or heterocyclic hybrid compounds. Various protocols are being followed to boost the pharmacological effects of PTP1B inhibitors. Moreover these new advancements suggest that it is possible to get small-molecule PTP1B inhibitors with the required potency and selectivity. Furthermore, future endevours via an integrated strategy of using medicinal chemistry and structural biology will hopefully result in potent and selective PTP1B inhibitors as well as safer and more effective orally available drugs.
Publikation

Hussain, H.; Abbas, G.; Green, I. R.; Ali, I.; Dipeptidyl peptidase IV inhibitors as a potential target for diabetes: patent review (2015-2018) Expert Opin. Ther. Pat. 29, 535-553, (2019) DOI: 10.1080/13543776.2019.1632290

Introduction: Dipeptidyl peptidase 4 (DPP-4) belongs to the family of serine proteases and is involved in the degradation of GLP-1 and GIP hormones, which enhance the production and release of insulin. Targeting DPP-4 inhibitors is increasingly being considered as promising paradigms to treat type 2 diabetes mellitus and therefore DPP-4 inhibitors are being considered as promising antidiabetic drugs.Areas covered: This review provides an overview of published patents describing natural and synthetic DPP-4 inhibitors from January 2015 to December 2018.Expert opinion: A fair number of new synthetic and natural DPP-4 inhibitors have been reported in last four years which describe the progress in the development of various heterocyclic scaffolds or heterocyclic hybrid compounds. As a result of this, many marketed DPP-4 inhibitors that have been approved by the appropriate governing bodies during the past decade, have been introduced as inhibitors. Molecular hybridization is an emerging idea in medicinal chemistry and therefore hybrid compounds of DPP-4 inhibitors with other DPP-4 inhibitors or with antidiabetic drugs should be formulated for a comprehensive evaluation. More detailed pharmacovigilance of DPP-4 inhibitors is required because this will address the pancreas-related adverse events as well as their impact on cardiovascular outcomes via long-term studies.
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