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A new compound, commikuanoid D, was isolated from the ethyl acetate fraction of Commiphora kua resin. The structure was unambiguously elucidated on the basis of complete spectroscopic analysis. Furthermore, the compound displayed potent carbonic anhydrase II inhibition with IC50 of 17.4 ± 0.32 μM. On the other hand, the molecular docking reflected that the acetyl group of the molecule specifically binds with the Zn ion at the active site of CA-II, and the OH group of the compound mediated hydrogen bonding with Gln92, thus blocking the enzyme activity with a good binding score (≥ 7 kcal/mol). [ABSTRACT FROM AUTHOR]

The ethyl acetate extract of the marine bacterial strain Streptomyces rochei sp. 81 was purified by silica gel column chromatography to obtain three diketopiperazines (1–3) and one straight chain fatty acid (4). The compounds were identified as cyclo(L-leu-N-ethenethiol-L-pro) (1), cyclo(L-Leu-L-Pro) (2), cyclo(L-Pro-D-Tyr) (3), and 2,4-dimethyldocasonoic acid (4) by HR-ESI-MS and NMR techniques. One new (1) and three known compounds (2–4) were screened for carbonic anhydrase-II (CA-II) inhibition and as a result 1 and 3 were found to be the most active compounds with IC50 of 9.8 ± 0.56 and 10.9 ± 0.88 μM, respectively. The results indicated that these two compounds (1 and 3) can be promising candidates for anticancer drugs. [ABSTRACT FROM AUTHOR]

In the current investigation, the chemical composition of the essential oils (EOs) from the stem and leaves of Acridocarpus orientalis A. Juss. were evaluated by gas chromatography (GC) and gas-chromatography-mass spectrometry (GC-MS). The main volatile constituents identified in the essential oil of stem were rich in methyl 8-pimaren-18-oate (43.8 %), octacosane (5.8 %), heptacosane (4.6 %) and hexacosane (4.1 %), methyl dehydroabietate (3.9 %) and methyl pimar-8(14)-en-18-oate (3.6 %), while tetracosane (16.6 %), heptacosane (16.4 %), docosane (13.9 %), hentriacontane (13.5 %), heneicosane (10.9 %) and α-pinene (7.7 %) were abundant in the EO of leaves. Both essential oils, screened against urease, α-glucosidase and carbonic anhydrase II (CA-II) enzyme inhibitory activities, were found active against CA-II and inactive against urease and α-glucosidase enzymes. The leaves of AO were found more active only against CA-II enzyme having IC50 values of 45.6 ± 1.0 μg/mL than stem (156.3 ± 1.5 μg/mL). The results determined that the EO of leaves could be a promising target for anti-cancer treatment. This is the first report, up to the best of the author's knowledge, on the chemical composition and CA-II activity of this essential oil. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Endophytic fungi are a substantial source of bioactive secondary metabolites. Present studies on Aspergillus nidulans-an endophytic fungus from Nyctanthes arbor-tristis Linn. afforded one new 1, 5-dihydroxy-3-methylxanthone-6-carboxylic acid methyl ester (1) and one known 5, 10-dihydro-phenazine-1-carboxylic acid (2) compound. The structures were elucidated by spectral techniques (Mass, 1D and 2D NMR), and their urease, carbonic anhydrase and prolyl endopeptidase inhibitory activities were evaluated. Compound 1 showed notable prolyl endopeptidase inhibition (IC50 = 3.13 ± 0.09 µM) and compound 2 showed significant carbonic anhydrase (IC50 =14.3 ± 1.05 µM) and urease (IC50 = 24.3 ± 1.15 µM) inhibition. [ABSTRACT FROM AUTHOR]

In several types of cancers, the expression of carbonic anhydrase-IX (CA-IX) enzyme is elevated than its normal level which ultimately plays a key role in the tumor growth of epithelial cells in breast and lung cancer by acidifying tumor microenvironment, therefore, inhibition of this target is important in antitumor therapy. We have synthesized bis -benzimidazole derivatives (1–25) by using 3,3′-diaminobenzidine and various aromatic aldehydes and characterized by various spectroscopic methods (UV/Visible, 1HNMR, 13CNMR, and mass spectrometry). Their inhibitory potential for human CA-IX (h CA-IX) was evaluated in-vitro , where several synthesized derivatives showed potent inhibition of h CA-IX (IC 50 values in range of 5.23 ± 1.05 to 40.10 ± 1.78 μM) and compounds 3–5 , 7–8 , 13–16 , 21 and 23 showed superior activity than the standard drug "acetazolamide" (IC 50 = 18.24 ± 1.43 μM). Furthermore, all these compounds showed no toxicity on human fibroblast cell lines (BJ cell lines). Moreover, molecular docking was carried out to predict their binding modes in the active site of CA-IX and revealed a significant role of imidazole ring of synthesized entities in their effective binding with the specific residues of CA-IX. The obtained results paved the way for further in vivo and other pharmacological studies for the optimization of these molecules as possible anti-cancer agents. [ABSTRACT FROM AUTHOR]

Diabetes mellitus, a progressive chronic disease, characterized by the abnormal carbohydrate metabolism is associated with severe health complications including long term dysfunction or failure of several organs, cardiovascular and micro-angiopathic problems (neuropathy, nephropathy, retinopathy). Despite the existence of diverse chemical structural libraries of α -glucosidase inhibitors, the limited diabetic treatment due to the adverse side effects such as abdominal distention, flatulence, diarrhoea, and liver damage associated with these inhibitors encourage the medicinal research community to design and develop new and potent inhibitors of α -glucosidase with better pharmacokinetic properties. In this perspective, we demonstrate the successful integration of common functional groups (ketone & ester) in one combined pharmacophore which is favorable for the formation of hydrogen bonds and other weaker interactions with the target proteins. These keto ester derivatives were screened for their α -glucosidase inhibition potential and the in vitro results revealed compound 3c as the highly active inhibitor with an IC 50 value of 12.4 ± 0.16 μM compared to acarbose (IC 50 = 942 ± 0.74 μM). This inhibition potency was ~76-fold higher than acarbose. Other potent compounds were 3f (IC 50 = 28.0 ± 0.28 μM), 3h (IC 50 = 33.9 ± 0.09 μM), 3g (IC 50 = 34.1 ± 0.04 μM), and 3d (IC 50 = 76.5 ± 2.0 μM). In addition, the emerging use of carbonic anhydrase inhibitors for the treatment of diabetic retinopathy (a leading cause of vision loss) prompted us to screen the keto ester derivatives for the inhibition of carbonic anhydrase-II. Compound 3b was found significantly active against carbonic anhydrase-II with an IC 50 of 16.5 ± 0.92 μM (acetazolamide; IC 50 = 18.2 ± 1.23 μM). Compound 3a also exhibited comparable potency with an IC 50 value of 18.9 ± 1.08 μM. Several structure-activity relationship analyses depicted the influence of the substitution pattern on both the aromatic rings. Molecular docking analysis revealed the formation of several H-bonding interactions through the ester carbonyl and the nitro oxygens of 3c with the side chains of His348, Arg212 and His279 in the active pocket of α -glucosidase whereas 3b interacted with His95, -OH of Thr197, Thr198 and WAT462 in the active site of carbonic anhydrase-II. Furthermore, evaluation of ADME properties suggests the safer pharmacological profile of the tested derivatives. The present study investigates the dual inhibitory potential of a series of keto ester derivatives against α -glucosidase and carbonic anhydrase-II enzymes. Unlabelled Image • New structural libraries of compounds were prepared to treat diabetes mellitus and diabetic retinopathy. • Keto esters 3a–m were investigated as potent inhibitors of α -glucosidase and carbonic anhydrase-II enzymes. • Compound 3c was identified as the most potent inhibitor of α -glucosidase enzyme. • Compound 3b inhibited the carbonic anhydrase-II with an IC 50 of 16.5 ± 0.92 μM. • Molecular docking, enzyme kinetics, and detailed ADMET properties were also investigated. [ABSTRACT FROM AUTHOR]

Three new cycloartane triterpenoids, commikuanoids A-C (1 – 3), together with four known compounds 4 – 7 , were isolated from the resin of Commiphora kua. Their structures were confirmed by advanced NMR techniques such as 1D (1H and 13C) and 2D (HMBC, HSQC, COSY, NOESY and NOE) and high-resolution mass spectrometry (HRMS). Five compounds (1 – 5) were screened for in vitro carbonic anhydrase II (CA II) inhibitory activity. All the tested compounds demonstrated significant activity against CA II with IC 50 values ranging from 4.9–19.6 μM. Moreover, the binding pattern of each compound in the binding site of CA-II was predicted through in silico molecular docking approach. It was observed that compounds 2 , 4 , and 5 binds with the Zn ion present in the active site of CA II, while compounds 1 and 3 mediated hydrogen bonding with Thr199 of CA-II, and all the compounds showed good binding score (> − 5 kcal/mol). [Display omitted] [ABSTRACT FROM AUTHOR]