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1.
Luogen Lai Qinqin Wang Binliang Zhang Zhen Xiao Zunhua Yang Qi Yang Zixin Luo Wufu Zhu Shan Xu 《RSC advances》2019,9(51):29579
A series of thienopyrimidines containing a pyrazoline unit (4a–d, 7a–d and 13a–l) were designed and synthesized. The target compounds were evaluated for antiproliferative activity against A549, HepG2 and MCF-7 cancer cell lines. Among the twenty target compounds, most of them exhibited excellent antiproliferative activity against one or several cancer cell lines. Compound 13f showed the best activity against A549, MCF-7 and HepG2 cancer cell lines, with IC50 values of 2.84 ± 0.09 μM, 2.88 ± 0.43 μM and 2.08 ± 0.36 μM, respectively. Four selected compounds (13c, 13f, 13g and 13h) were further evaluated for their inhibitory activity against the PI3Kα/mTOR protein kinase. Moreover, time-dependent and dose-dependent experiments, AO fluorescence staining, Annexin V-FITC/PI staining and docking studies were carried out in this study. The results indicated that compound 13f may be a potential selective PI3Kα inhibitor.A series of thienopyrimidines containing a pyrazoline unit (4a–d, 7a–d and 13a–l) were designed and synthesized. The compound 13f showed the best activity with the IC50 of 0.92 μM against PI3Kα. 相似文献
2.
Meng-Xue Wei Jia-Ying Yu Xin-Xin Liu Xue-Qiang Li Jin-Hui Yang Meng-Wei Zhang Pei-Wen Yang Si-Si Zhang Yu He 《RSC advances》2021,11(30):18333
For the first time, six novel artemisone–piperazine–tetronamide hybrids (12a–f) were efficiently synthesised from dihydroartemisinin (DHA) and investigated for their in vitro cytotoxicity against some human cancer cells and benign cells. All the targets showed good cytotoxic activity in vitro. Hybrid 12a exhibited much better inhibitory activity against human liver cancer cell line SMMC-7721 (IC50 = 0.03 ± 0.04 μM for 24 h) than the parent DHA (IC50 > 0.7 μM), and two references, vincristine (VCR; IC50 = 0.27 ± 0.03 μM) & cytosine arabinoside (ARA; IC50 = 0.63 ± 0.04 μM). Furthermore, hybrid 12a had low toxicity against human benign liver cell line LO2 (IC50 = 0.70 ± 0.02 μM for 24 h) compared with VCR, ARA, and DHA in vitro. Moreover, the inhibitory activity of hybrid 12a was obviously enhanced when human liver cancer cell line MHCC97H absorbed Fe2+in vitro.Six novel artemisone–piperazine–tetronamide hybrids were efficiently synthesised and investigated for their cytotoxicity against some human cancer cells. 相似文献
3.
The current optimization of tetrazanbigen (TNBG) on the C-ring provided a series of new sterol derivatives 2a–2n. All new synthesized compounds were screened for their anti-proliferation activities against five human cancer cell lines (HepG2, QGY-7701, SMMC-7721, A-431 and NCI-H23 cell lines) in vitro. Among them, 2a, 2b, 2c, 2m and 2n exhibited high anti-proliferation activities on SMMC-7721, and their IC50 values approach that of the positive control drug cisplatin. Compound 2a not only showed strong anti-proliferation activities against QGY-7701 and HepG2 cell lines, with IC50 values (IC50: 6.81 ± 0.24 μM, 7.69 ± 0.87 μM) better than that of cisplatin (IC50: 8.75 μM, 18.89 ± 2.01 μM), but also exhibited good aqueous solubility (0.15–15 mg mL−1 at pH 7.4 and 2.0). On the most sensitive QGY-7701 cell line, Oil red O staining and western blot analysis were performed. The results suggested that 2a can inhibit the growth of cancer cells possibly by interfering with the lipid metabolism balance of tumor cells, resulting in lipid accumulation and cell apoptosis (lipotoxicity). Moreover, after being treated with 2a, lipid accumulation of QGY-7701 cell was increased in a time and dose dependent manner. Based on these promising results, 2a was selected for drug formulation and further pre-clinical development.The current optimization of tetrazanbigen (TNBG) on the C-ring provided a series of new sterol derivatives 2a–2n. 相似文献
4.
Dina H. Dawood Aladdin M. Srour Dalia O. Saleh Kelley J. Huff Francesca Greco Helen M. I. Osborn 《RSC advances》2021,11(47):29441
Based on studies that have reported the association between cancer and cardiovascular diseases, new series of pyridine- (3a–o) and/or chromene- (4a–e) carbonitrile analogous were designed, synthesized and screened for their vasodilation and cytotoxic properties. The majority of the new chemical entities demonstrated significant vasodilation efficacies, compounds 3a, 3h, 3j, 3m, 3o, 4d and 4e exhibited the most promising potency with IC50 = 437.9, 481.0, 484.5, 444.8, 312.1, 427.6 and 417.2 μM, respectively, exceeding prazosin hydrochloride (IC50 = 487.3 μM). Compounds 3b–e, 3k and 3l also, revealed moderate vasodilation activity with IC50 values ranging from 489.7 to 584.5 μM. In addition, the anti-proliferative activity evaluation of the experimental compounds at 10 μM on the MCF-7 and MDA-MB 231 breast cancer cell lines illustrated the excellent anti-proliferative properties of derivatives 3d, 3g and 3i. Compound 3d was the most potent analogue with IC50 = 4.55 ± 0.88 and 9.87 ± 0.89 μM against MCF-7 and MDA-MB 231, respectively. Moreover, compound 3d stimulated apoptosis and cell cycle arrest at the S phase in MCF-7 cells in addition to its capability in accumulation of cells in pre-G1 phase and activating caspase-3. Furthermore, the molecular docking of 3d was performed to discover the binding modes within the active site of caspase-3. 3d, as the only common bi-functional agent among the tested hits, demonstrated that new pyridine-3-carbonitrile derivatives bearing cycloheptyl ring systems offer potential as new therapeutic candidates with combined vasodilation and anticancer properties.Series of pyridine- (3a–o) and/or chromene- (4a–e) carbonitrile scaffolds have been designed, synthesized and evaluated for their bi-function activities, 3d was the only common derivative having combined vasodilation and anticancer properties. 相似文献
5.
Noman Javid Saquib Jalil Rubina Munir Muhammad Zia-ur-Rehman Amna Sahar Sara Arshad Jamshed Iqbal 《RSC advances》2023,13(3):1701
Two series of new 2,1-benzothiazine derivatives have been synthesized by condensation of 4-hydrazono-1-methyl-3,4-dihydro-1H-benzo[c][1,2]thiazine 2,2-dioxide (5) with 2-chloroquinoline-3-carbaldehydes and acetylthiophenes to acquire new heteroaryl ethylidenes 7(a–f) and 9(a–k) in excellent yields. After characterization by FTIR, 1H NMR, 13C NMR and elemental analyses, the newly synthesized analogues were investigated against monoamine oxidase enzymes (MAO A and MAO B). The titled compounds exhibited activity in the lower micromolar range among which 9e was the most potent compound against MAO A with IC50 of 1.04 ± 0.01 μM whereas 9h proved to be the most potent derivative against MAO B with an IC50 value of 1.03 ± 0.17 μM. Furthermore, in vitro results were further endorsed by molecular docking studies to determine the interaction between the potent compounds and the enzyme active site. These newly synthesized compounds represent promising hits for the development of safer and potent lead molecules for therapeutic use against depression and other neurological diseases.Two series of new 2,1-benzothiazine-heteroaryl ethylidene derivatives 7(a–f) and 9(a–k) have been synthesized in excellent yields and tested against MAOs. 相似文献
6.
Tran Thi Phuong Thao Thanh Q. Bui Nguyen Thi Thanh Hai Lam K. Huynh Phan Tu Quy Nguyen Chi Bao Nguyen Thi Dung Nguyen Linh Chi Tran Van Loc Irina E. Smirnova Anastasiya V. Petrova Pham Thi Ninh Tran Van Sung Nguyen Thi Ai Nhung 《RSC advances》2021,11(57):35765
Dipterocarpus alatus-derived products are expected to exhibit anti-diabetes properties. Natural dipterocarpol (1) was isolated from Dipterocarpus alatus collected in Quang Nam province, Vietnam; afterwards, 20 derivatives including 13 oxime esters (2 and 3a–3m) and 7 lactones (4, 5, 6a–6e) were semi-synthesised. Their inhibitory effects towards diabetes-related proteins were investigated experimentally (α-glucosidase) and computationally (3W37, 3AJ7, and PTP1B). Except for compound 2, the other 19 compounds (3a–3m, 4, 5, and 6a–6d) are reported for the first time, which were modified at positions C-3, C-24 and C-25 of the dipterocarpol via imidation, esterification, oxidative cleavage and lactonisation reactions. A framework based on docking-QSARIS combination was proposed to predict the inhibitory behaviour of the ligand-protein complexes. Enzyme assays revealed the most effective α-glucosidase inhibitors, which follow the order 5 (IC50 of 2.73 ± 0.05 μM) > 6c (IC50 of 4.62 ± 0.12 μM) > 6e (IC50 of 7.31 ± 0.11 μM), and the computation-based analysis confirmed this, i.e., 5 (mass: 416.2 amu; polarisability: 52.4 Å3; DS: −14.9 kcal mol−1) > 6c (mass: 490.1 amu; polarisability: 48.8 Å3; DS: −13.7 kcal mol−1) > 6e (mass: 549.2 amu; polarisability: 51.6 Å3; DS: −15.2 kcal mol−1). Further theoretical justifications predicted 5 and 6c as versatile anti-diabetic inhibitors. The experimental results encourage next stages for the development of anti-diabetic drugs and the computational strategy invites more relevant work for validation. Dipterocarpus alatus-derived products are expected to exhibit anti-diabetes properties. 相似文献
7.
Jamshaid Ashraf Ehsan Ullah Mughal Reem I. Alsantali Amina Sadiq Rabab. S. Jassas Nafeesa Naeem Zaman Ashraf Yasir Nazir Muhammad Naveed Zafar Amara Mumtaz Masoud Mirzaei Satar Saberi Saleh A. Ahmed 《RSC advances》2021,11(56):35077
The excelling role of organic chemistry in the medicinal field continues to be one of the main leads in the drug development process. Particularly, this industry requires organic chemists to discover small molecular structures with powerful pharmacological potential. Herein, a diverse range of chalcone (1–11) and aurone (12–22) derivatives was designed and synthesized and for the first time, and both motifs were evaluated as potent inhibitors of alkaline phosphatases (APs). Structural identification of the target compounds (1–22) was accomplished using common spectroscopic techniques. The effect of the nature and position of the substituent was interestingly observed and justified based on the detailed structure–activity relationship (SAR) of the target compounds against AP. It was concluded from the obtained results that all the newly synthesized compounds exhibit high inhibitory potential against the AP enzyme. Among them, compounds 12 (IC50 = 2.163 ± 0.048 μM), 15 (IC50 = 2.146 ± 0.056 μM), 16 (IC50 = 2.132 ± 0.034 μM), 18 (IC50 = 1.154 ± 0.043 μM), 20 (IC50 = 1.055 ± 0.029 μM) and 21 (IC50 = 2.326 ± 0.059 μM) exhibited excellent inhibitory activity against AP, and even better/more active than KH2PO4 (standard) (IC50 = 2.80 ± 0.065 μM). Remarkably, compound 20 (IC50 = 1.055 ± 0.029 μM) may serve as a lead structure to design more potent inhibitors of alkaline phosphatase. To the best of our knowledge, these synthetic compounds are the most potent AP inhibitors with minimum IC50 values reported to date. Furthermore, a molecular modeling study was performed against the AP enzyme (1EW2) to check the binding interaction of the synthesized compounds 1–22 against the target protein. The Lineweaver–Burk plots demonstrated that most potential derivative 20 inhibited h-IAP via a non-competitive pathway. Finally, molecular dynamic (MD) simulations were performed to evaluate the dynamic behavior, stability of the protein–ligand complex, and binding affinity of the compounds, resulting in the identification of compound 20 as a potential inhibitor of AP. Accordingly, excellent correlation was observed between the experimental and theoretical results. The pharmacological studies revealed that the synthesized analogs 1–22 obey Lipinski''s rule. The assessment of the ADMET parameters showed that these compounds possess considerable lead-like characteristics with low toxicity and can serve as templates in drug design.Aurones are the plant secondary metabolites belonging to the flavonoid’s family. The bioactivities of aurones are very promising, thus these heterocyclic compounds can be considered as an alluring scaffold for drug design and development. 相似文献
8.
Eleven new 9,19-cycloartane triterpenes (1–9, 11–12) and one undescribed lanostane-type aglycone (10) were identified from the aerial parts of Cimicifuga yunnanensis. The new structures were elucidated by analysis of spectroscopic data. Compounds 3–5, 7–9, and 11, without obvious cytotoxicity at 50 μM, were evaluated for inhibiting the mRNA expressions of atherosclerosis-related factors of CD147 (extracellular matrix metalloproteinase inducer, EMMPRIN), matrix metalloproteinase 2 (MMP-2) and MMP-9 in phorbol-12-myristate-13-acetate (PMA) induced Human monocytic THP-1 cells by using a quantitative real-time PCR method (q-PCR). Among them, aglycones 7 and 8 showed potent activities, whereas all tested glycosides were inactive. Compounds 7 and 8 suppressed the mRNA expression of CD147 in a dose-dependent manner, with an IC50 value of 3.38 ± 0.27 μM and 8.25 ± 0.33 μM, respectively. Besides, 7 dose-related down-regulated the mRNA expression of MMP-2, and MMP-9, having an IC50 value of 6.32 ± 0.31 μM and 11.57 ± 0.23 μM, respectively. Meanwhile, 8 at 10 μM reduced the mRNA expression of MMP-2 and MMP-9 by 35% and 25%, respectively. Significantly, the migration ability of the induced THP-1 cells was potently and dose-dependently inhibited by 7, with an IC50 value of 5.87 ± 0.27 μM.Eleven new 9,19-cycloartane triterpenes (CTs) (1–9, 11–12) and one undescribed lanostane-type aglycone (10) were identified from Cimicifuga yunnanensis. CTs aglycones 7 and 8 potently down-regulated the mRNA expression of CD147, MMP-2, and MMP-9. 相似文献
9.
Dong-Mei Sun Fa-Liang An Shan-Shan Wei Yan-Qiu Zhang Xiao-Bing Wang Jun Luo Ling-Yi Kong 《RSC advances》2018,8(19):10437
Eleven new mexicanolide-type limonoids, cipadessains A–K (1–11), were isolated from the fruits of Cipadessa cinerascens (Pellegr) Hand.-Mazz. Their planar structures were determined based on IR, UV, 1D and 2D NMR spectra and HRESIMS data. The absolute configuration of 1 was elucidated by single-crystal X-ray diffraction using mirror Cu Kα radiation, and that of compounds 2–8 were determined by ECD analysis. Two mexicanolides bearing methoxybutenolide moiety originated from the furan ring 3 and 6, showed significant cytotoxicity against HepG2 cell line with IC50 values of 5.23 ± 0.12, 8.67 ± 1.02 μM, respectively; and NO inhibitory activities in LPS-activated RAW 264.7 macrophages at nontoxic concentration (IC50 5.79 ± 0.18, 6.93 ± 0.89 μM, respectively).Eleven new mexicanolide-type limonoids, cipadessains A–K (1–11), were isolated from the fruits of Cipadessa cinerascens (Pellegr) Hand.-Mazz. 相似文献
10.
Noor Fathima Anjum Dhivya Shanmugarajan Vasanth Kumar Shivaraju Syed Faizan Namburu Lalitha Naishima B. R. Prashantha Kumar Saleem Javid Madhusudan N. Purohit 《RSC advances》2022,12(26):16966
Eugenol is a natural product abundantly found in clove buds known for its pharmacological activities such as anti-inflammatory, antidiabetic, antioxidant, and anticancer activities. It is well known from the literature that peroxisome proliferator-activated receptors (PPARγ) have been reported to regulate inflammatory responses. In this backdrop, we rationally designed semi-synthetic derivatives of eugenol with the aid of computational studies, and synthesized, purified, and analyzed four eugenol derivatives as PPARγ agonists. Compounds were screened for PPARγ protein binding by time-resolved fluorescence (TR-FRET) assay. The biochemical assay results were favorable for 1C which exhibited significant binding affinity with an IC50 value of 10.65 μM as compared to the standard pioglitazone with an IC50 value of 1.052 μM. In addition to the protein binding studies, as a functional assay, the synthesized eugenol derivatives were screened for in vitro anti-inflammatory activity at concentrations ranging from 6.25 μM to 400 μM. Among the four compounds tested 1C shows reasonably good anti-inflammatory activity with an IC50 value of 133.8 μM compared to a standard diclofenac sodium IC50 value of 54.32 μM. Structure–activity relationships are derived based on computational studies. Additionally, molecular dynamics simulations were performed to examine the stability of the protein–ligand complex, the dynamic behavior, and the binding affinity of newly synthesized molecules. Altogether, we identified novel eugenol derivatives as potential anti-inflammatory agents via PPARγ agonism.Rational design, synthesis, analysis, PPARγ protein binding assay and computational studies of novel eugenol derivatives. 相似文献
11.
Versiquinazolines L–Q,new polycyclic alkaloids from the marine-derived fungus Aspergillus versicolor
Further chemical examination of a coral-associated fungus Aspergillus versicolor LZD-14-1 by the PHLC-DAD detection resulted in the isolation of six new polycyclic alkaloids, namely versiquinazolines L–Q (1–6). Their structures were determined by extensive analyses of spectroscopic data, including quantum ECD calculation and X-ray single crystal diffraction for the assignment of absolute configurations. Versiquinazoline L bearing a d-Ala residue and versiquinazoline M containing an l-serine residue are rarely found in the fumiquinazoline-type alkaloids, while versiquinazoline P displayed an unusual scaffold with a spiro-γ-lactone. Versiquinazolines P and Q exhibited significant inhibition against thioredoxin reductase (TrxR) with IC50 values of 13.6 ± 0.6 and 12.2 ± 0.7 μM, which showed higher activity than the positive control curcumin (IC50 = 25 μM). The weak cytotoxicity and potent inhibition toward TrxR suggested that versiquinazolines P and Q are potential for microenvironmental regulation of tumor progression and metastasis.Further chemical examination of a coral-associated fungus Aspergillus versicolor LZD-14-1 by the PHLC-DAD detection resulted in the isolation of six new polycyclic alkaloids, namely versiquinazolines L–Q (1–6). 相似文献
12.
Chindawadee Chuenban Aonnicha Sombatsri Thurdpong Sribuhom Chanakan Pornchoo Auemduan Prawan Sarawut Tontapha Vittaya Amornkitbamrung Chavi Yenjai 《RSC advances》2021,11(7):4097
Six undescribed polyketides, 1–6, were discovered from the fruits of Knema globularia (Lam.) warb. Two known polyketides and three known lignans were also isolated. Cytotoxicities against HepG2 and KKU-M156 cells of all polyketides were evaluated. Compound 1 displayed the most cytotoxic activity against HepG2 and KKU-M156 cell lines with IC50 values of 1.57 ± 0.37 and 1.78 ± 0.14 μg mL−1, respectively. The structure of all isolates was identified using spectroscopic methods including NMR, IR, MS and ECD.Compound 1 displayed the most cytotoxic activity against HepG2 and KKU-M156 cell lines with IC50 values of 1.57 ± 0.37 and 1.78 ± 0.14 μg mL−1, respectively. 相似文献
13.
In this study, a variety of nanocomposites, namely, MEL@AgNPs, MEL@ZnONPs, and Ag–ZnO/MEL/GA were biosynthesized using MEL and gum arabic to serve in biomedical applications. The synthesized nanocomposites were examined using X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and FTIR spectroscopy. The physicochemical properties and biomedical activities of the synthesized nanocomposites were investigated. The Ag–ZnO/MEL/GA nanocomposites showed greater antidiabetic activity against α-amylase and α-glucosidase, and higher antibacterial activity compared to MEL@AgNPs and MEL@ZnONPs. Furthermore, HepG2 cells were exposed to MEL@AgNPs, MEL@ZnONPs, and Ag–ZnO/MEL/GA nanocomposites for 24 h and their IC50 values were 63.25, 26.91 and 28.97 μg mL−1 (P < 0.05), respectively. According to this comparative study, it is apparent that the Ag–ZnO/MEL/GA nanocomposites have a great potential to serve as antitumor agents against HepG2, and antidiabetic and antibacterial agents.MEL@AgNPs, MEL@ZnONPs, and Ag–ZnO/MEL/GA nanocomposites were successfully prepared by using mannosylerythritol lipids (MEL) and gum arabic. 相似文献
14.
Muhammad Aamer Mahwish Siddiqui Almas Jabeen Rimsha Irshad Farooq-Ahmad Khan Atia-tul-Wahab M. Iqbal Choudhary Yan Wang 《RSC advances》2022,12(15):9494
An anabolic-androgenic synthetic steroidal drug, methasterone (1) was transformed by two fungi, Cunninghamella blakesleeana and Macrophimina phaseclina. A total of six transformed products, 6β,7β,17β-trihydroxy-2α,17α-dimethyl-5α-androstane-3-one (2), 6β,7α,17β-trihydroxy-2α,17α-dimethyl-5α-androstane-3-one (3), 6α,17β-dihydroxy-2α,17α-dimethyl-5α-androstane-3,7-dione (4), 3β,6β,17β-trihydroxy-2α,17α-dimethyl-5α-androstane-7-one (5), 7α,17β-dihydroxy-2α,17α-dimethyl-5α-androstane-3-one (6), and 6β,9α,17β-trihydroxy-2α,17α-dimethyl-5α-androstane-3-one (7) were synthesized. Among those, compounds 2–5, and 7 were identified as new transformed products. MS, NMR, and other spectroscopic techniques were performed for the characterization of all compounds. Substrate 1 (IC50 = 23.9 ± 0.2 μg mL−1) showed a remarkable anti-inflammatory activity against nitric oxide (NO) production, in comparison to standard LNMMA (IC50 = 24.2 ± 0.8 μg mL−1). Whereas, its metabolites 2, and 7 showed moderate inhibition with IC50 values of 38.1 ± 0.5 μg mL−1, and 40.2 ± 3.3 μg mL−1, respectively. Moreover, substrate 1 was found to be cytotoxic for the human normal cell line (BJ) with an IC50 of 8.01 ± 0.52 μg mL−1, while metabolites 2–7 were identified as non-cytotoxic. Compounds 1–7 showed no cytotoxicity against MCF-7 (breast cancer), NCI-H460 (lung cancer), and HeLa (cervical cancer) cell lines.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. 相似文献
15.
Morbidity and mortality due to hepatitis C virus (HCV) is a globe health concern. Hence, there is a persistent demand to design and optimize current HCV therapy and develop novel agents. HCV NS3/A4 protease plays an essential role in HCV life cycle and replication. Thus, HCV NS3/A4 protease inhibitors are one of the best therapeutic targets for the identification of novel candidate drugs. Recent studies have shown some benzoquinazolines as potent antiviral agents and promising HAV-3C protease inhibitors. In the present study, a series of benzo[g]quinazolines (1–13) and their quinazoline analogues (14–17) were evaluated for their HCV-NS3/4A inhibitory activities using in vitro assay. Our results revealed that the target compounds inhibited the activity of the NS3/4A enzyme, (IC50 = 6.41 ± 0.12 to 78.80 ± 1.70 μM) in comparison to telaprevir (IC50 = 1.72 ± 0.03 μM) as a reference drug. Compounds 1, 2, 3, 9, 10 and 13 showed the highest activity (IC50 = 11.02 ± 0.25, 6.41 ± 0.12, 9.35 ± 0.19, 9.08 ± 0.20, 16.03 ± 0.34 and 7.21 ± 0.15 μM, respectively). Molecular docking was performed to study the binding modes of the docked-chosen benzo[g]quinazolines, hydrogen bonding, and amino acid residues at the catalytic triad of the NS3/4A enzyme of HCV. The QSAR was determined to explore the relationships between the molecular structures of the targets and their biological activities by developing prediction models among the known HCV NS3/A4 inhibitors and then to predict the inhibitory activity of the target molecules synthesized.HCV NS3/A4 protease inhibitors are one of the best therapeutic targets for the identification of novel candidate drugs. A series of benzo[g]quinazolines and their quinazoline analogues were evaluated for their HCV-NS3/4A inhibitory activities. 相似文献
16.
Mahendra Gowdru Srinivasa Jagdish Gopal Paithankar Sumit Rao Saheb Birangal Aravinda Pai Vasudev Pai Shridhar N. Deshpande B. C. Revanasiddappa 《RSC advances》2023,13(3):1567
As compared to standard medicinal compounds, hybrid molecules that contain multiple biologically active functional groups have greater affinity and efficiency. Hence based on this concept, we predicted that a combination of thiazolidinediones and 1,3,4-oxadiazoles may enhance α-amylase and α-glucosidase inhibition activity. A series of novel 3-((5-phenyl-1,3,4-oxadiazol-2-yl)methyl)thiazolidine-2,5-dione derivatives (5a–5j) were synthesized and characterized using different spectroscopic techniques i.e., FTIR, 1H-NMR, 13C-NMR and MS. To evaluate in silico, molecular docking, MMGBSA, and MD simulations were carried out which were further evaluated via in vitro inhibition of α-amylase and α-glycosidase enzyme inhibition assays. In addition, the in vivo study was performed on a genetic model of Drosophila melanogaster to assess the antihyperglycemic effects. The compounds (5a–5j) demonstrated α-amylase and α-glucosidase inhibitory activity in the range of IC50 values 18.42 ± 0.21–55.43 ± 0.66 μM and 17.21 ± 0.22–51.28 ± 0.88 μM respectively when compared to standard acarbose. Based on the in vitro studies, compounds 5a, 5b, and 5j were found to be potent against both enzymes. In vivo studies have shown that compounds 5a, 5b, and 5j lower glucose levels in Drosophila. These compounds could be further developed in the future to produce a new class of antidiabetic agents.As compared to standard medicinal compounds, hybrid molecules that contain multiple biologically active functional groups have greater affinity and efficiency. 相似文献
17.
Supakorn Arthan Priyapan Posri Sookkawath Walunchapruk Thanaset Senawong Chavi Yenjai 《RSC advances》2022,12(28):17837
Fifteen derivatives were synthesized from olibergin A, a major isoflavonoid isolated from the stems of Dalbergia stipulacea Roxb. All compounds were evaluated for cytotoxicity against HCT-116, HT-29, MCF-7 and vero cell lines using MTT assay. Cytotoxicity results showed 5-hydroxy-7,2′,4′,5′-tetramethoxyisoflavone (5) was the most active with IC50 values of 19.03 ± 0.70, 10.83 ± 1.65, 12.53 ± 0.70 and 13.53 ± 0.84 μM against HCT-116, HT-29, MCF-7 and vero cell lines, respectively. It should be noted that 5-hydroxy-7,2′,4′,5′-tetramethoxyisoflavone (5) showed two times less toxicity against vero cells than the cisplatin standard (IC50 = 6.55 ± 0.81 μM) while 5 and cisplatin exhibited nearly equal cytotoxicity against the MCF-7 cell line. 5,7,2′,4′,5′-Pentamethoxyisoflavanone (10) showed an IC50 value of 30.34 ± 1.15 μM against the HCT-116 cell line and exhibited weak cytotoxicity against normal cells, the vero cell line. In addition, 5,7,4′-trihydroxy-2′,5′-dimethoxyisoflavan oxime (13) demonstrated cytotoxicity against HT-29 cells with an IC50 value of 31.41 ± 1.38 μM and displayed weak activity toward the vero cell line. The information revealed that these compounds were suitable for development to anticancer agents against HCT-116, HT-29 and MCF-7 cell lines.Fifteen derivatives were synthesized from olibergin A, a major isoflavonoid isolated from the stems of Dalbergia stipulacea Roxb. 相似文献
18.
Nour E. A. Abd El-sattar Eman H. K. Badawy Eman Z. Elrazaz Nasser S. M. Ismail 《RSC advances》2021,11(8):4454
Poly(ADP-ribose) polymerases-1 (PARP-1) are involved in DNA repair damage and so PARP-1 inhibitors have been used as potentiators in combination with DNA damaging cytotoxic agents to compromise the cancer cell DNA repair mechanism, resulting in genomic dysfunction and cell death. In this study, we report the synthesis of a novel series of pyrano[2,3-d]pyrimidine-2,4-dione analogues as potential inhibitors against PARP-1. All the newly synthesized compounds were evaluated for their inhibitory activity towards PARP-1 and examined for their anti-proliferative activity against MCF-7 and HCT116 human cancer cell lines. The synthesized compounds showed promising activity where compounds S2 and S7 emerged as the most potent PARP-1 inhibitors with an IC50 value of 4.06 ± 0.18 and 3.61 ± 0.15 nM, respectively compared to that of Olaparib 5.77 nM and high cytotoxicity against MCF-7 with IC50 2.65 ± 0.05 and 1.28 ± 1.12 μM, respectively (Staurosporine 7.258 μM). Compound S8 remarkably showed the highest cell growth inhibition against MCF-7 and HCT116 with an IC50 value of 0.66 ± 0.05 and 2.76 ± 0.06 μM, respectively. Furthermore, molecular docking of the compounds into the PARP-1 active site was performed to explore the probable binding mode. Finally, most of the synthesized compounds were predicted to have good pharmacokinetics properties in a theoretical kinetic study.PARP-1 are involved in DNA repair damage and so PARP-1 inhibitors have been used as potentiators in combination with DNA damaging cytotoxic agents to compromise the cancer cell DNA repair mechanism, resulting in genomic dysfunction and cell death. 相似文献
19.
Bioassay-guided investigation of Panicum turgidum extract resulted in the identification of seven steroidal saponins (Turgidosterones 1–7). They were evaluated for their in vitro antifungal, antileishmanial, and antitrypanosomal activities. Turgidosterone 6 was the most active antifungal against Candida albicans and Candida neoformans (IC50 values of 2.84 and 1.08 μg mL−1, respectively). Turgidosterones 4–7 displayed antileishmanial activity against Leishmania donovani promastigotes with IC50 values ranging from 4.95 to 8.03 μg mL−1 and against Leishmania donovani amastigote/THP with IC50 values range of 4.50–9.29 μg mL−1. Activity against Trypanosoma brucei was also observed for Turgidosterones 4–7 with an IC50 values range of 1.26–3.77 μg mL−1. Turgidosterones 1–3 did not display any activity against the tested pathogens. The study of structure–activity relationships of the isolated saponins indicated that the antifungal, antileishmanial, and antitrypanosomal activities are markedly affected by the presence of spirostane-type saponins and the elongation of the sugar residue at C-3. To quantitatively determine the most abundant active ingredient in Panicum turgidum extract, a single run, sensitive, and highly selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been applied under positive and negative modes. The obtained results showed that compound 5 was the most abundant (95.93 ± 1.10 mg per gram of dry Panicum turgidum extract), followed by 6 (52.51 ± 1.05 mg gm−1), 4 (32.71 ± 0.48 mg gm−1), and 7 (13.19 ± 0.50 mg gm−1). Docking of these saponins against the Candida albicans oxidoreductases and Leishmania infantum trypanothione reductase active sites revealed their potential to effectively bind with a number of key residues in both receptor targets.Bioassay-guided investigation of Panicum turgidum extract resulted in the identification of seven steroidal saponins (Turgidosterones 1–7). 相似文献
20.
Ahmed H. Tantawy Xiang-Gao Meng Adel A. Marzouk Ali Fouad Ahmed H. Abdelazeem Bahaa G. M. Youssif Hong Jiang Man-Qun Wang 《RSC advances》2021,11(41):25738
A series of novel piperine–resveratrol hybrids 5a–h was designed, synthesized, and structurally elucidated by IR, and 1H, 13C, and 19F NMR. Antiproliferative activities of 5a–h were evaluated by NCI against sixty cancer cell lines. Compound 5b, possessing resveratrol pharmacophoric phenolic moieties, showed a complete cell death against leukemia HL-60 (TB) and Breast cancer MDA-MB-468 with growth inhibition percentage of −0.49 and −2.83, respectively. In addition, 5b recorded significant activity against the other cancer cell lines with growth inhibition percentage between 80 to 95. New 5a–h hybrids were evaluated for their inhibitory activities against Sirt-1 and Sirt-2 as molecular targets for their antiproliferative action. Results showed that compounds 5a–h were more potent inhibitors of Sirt-2 than Sirt-1 at 5 μm and 50 μm. Compound 5b showed the strongest inhibition of Sirt-2 (78 ± 3% and 26 ± 3% inhibition at 50 μM and 5 μM, respectively). Investigation of intermolecular interaction via Hirschfeld surface analysis indicates that these close contacts are mainly ascribed to the O–H⋯O hydrogen bonding. To get insights into the Sirt-2 inhibitory mechanism, a docking study was performed where 5b was found to fit nicely inside both extended C-pocket and selectivity pocket and could compete with the substrate acyl-Lys. Another possible binding pattern showed that 5b could act by partial occlusion of the NAD+ C-pocket. Collectively, these findings would contribute significantly to better understanding the Sirt-2 inhibitory mechanism in order to develop a new generation of refined and selective Sirt-2 inhibitors.A series of novel piperine–resveratrol hybrids 5a–h was designed, synthesized, and structurally elucidated by IR, and 1H, 13C, and 19F NMR. 相似文献