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1.
Navudu Ramesh Mannem Gangadhara Rao Ravi Varala V. Umamaheswra Rao B. Hari Babu 《Medicinal chemistry research》2016,25(9):1945-1951
A series of ten 2,3-dihydroquinizolin-4(1H)-one derivatives were synthesized by ethanol-mediated condensation of anthranilamide with various aryl aldehydes in presence of catalytic amount of mercuric chloride (HgCl2). The temperature of the reactions was maintained at 60?°C for good yield of the products. The highlights of the method include use of lab grade of chemicals as reagents and ease of work up in obtaining the product with high purity. Out of ten derivatives synthesized, three compounds 3f, 3i, and 3j are new and all the compounds were evaluated for their cytotoxic activity against six cancer cell lines. The compounds 3b (IC50: 26.1?µg mL?1), 3c (42.7?µg mL?1) ,and 3e (31.1?µg mL?1) have shown activity against the cell line MDA-MB-231. Compounds 3b, 3c, 3d, 3e, and 3g showed significant total growth inhibition (TGI) values against the cell line MDA-MB-231 and compound 3j showed good TGI value against the cell line PANC 1. Compounds were also screened for their antibacterial activity and antioxidant activity by DPPH method. 相似文献
2.
Santhosh Subramanian Pulla Reddy Boggu Jieun Yun Sang-Hun Jung 《Archives of pharmacal research》2018,41(3):251-258
For confirming the role of five membered ring of imidazolidinone moiety of N-arylsulfonylimidazolidinones (7) previously reported with highly potent anticancer agent, a series of N-arylsulfonylpyrimidones (10a–g) and N-arylsulfonyltetrahydropyrimidones (11a–e) were prepared and their anti-proliferating activity was measured against human cancer cell lines (renal ACHN, colon HCT-15, breast MDA-MB-231, lung NCI-H23, stomach NUGC-3, and prostate PC-3) using XTT assay. Among them, 1-(1-acetylindolin-5-ylsulfonyl)-4-phenyltetrahydropyrimidin-2(1H)-one (11d, mean GI50 = 3.50 µM) and ethyl 5-(2-oxo-4-phenyltetrahydropyrimidin-1(2H)-ylsulfonyl)-indoline-1-carboxylate (11e, mean GI50 = 0.26 µM) showed best growth inhibitory activity against human cancer cell lines. Considering the activity results, N-arylsulfonyltetrahydropyrimidones (11) exhibited more potent activity compared to N-arylsulfonylpyrimidones (10) and comparable activity to N-arylsulfonylimidazolidinones (7). Especially, tetrahydropyrimidin-2(1H)-one analogs containing acylindolin-5-ylsulfonyl moiety at position 1 demonstrated their strong growth inhibitory activity against human cancer cell lines. 相似文献
3.
M. S. R. Murty Raju Penthala Sowjanya Polepalli N. Jain 《Medicinal chemistry research》2016,25(4):627-643
A novel class of resveratrol-oxadiazole hybrid compounds was synthesized to screen for their in vitro antiproliferative activity against three human cancer cell lines. All the compounds showed superior antiproliferative activity than the reference compound resveratrol. The most promising active compounds in this series were 1g, 2g, 1c, 2c, 2i and 1a (GI50 < 0.1 µM), endowed with excellent antiproliferative activity. Thus, we believe that resveratrol-oxadiazole hybrid compounds may possibly be used as a good leads for the development of new antiproliferative agents. Structures of newly synthesized compounds were confirmed by NMR and IR spectral data. 相似文献
4.
Some novel thiophene and theinopyrimidine derivatives have been synthesized. Their structures were confirmed by elemental analyses, infrared, 1H NMR, 13C NMR and mass spectral data. All the target compounds were screened against liver adenocarcinoma (HepG2) cell line. Compounds 9c, 9b, 10b, and 7c in a sequent were the most potent compounds between all the test compounds with IC50 values [0.01063, 0.01158, 0.01729, 0.01957?µM], respectively. Compounds 13b, 7b, 5d, 9a, 8a, and 11b showed higher activity with IC50 values ranged from 0.02231 to 0.03673?µM when compared with 5-flurouracil (A) as a reference drug (IC50?=?0.0384?µM). 相似文献
5.
Rafat M. Mohareb Rehab A. Ibrahim Wagnat W. Wardakhan 《Medicinal chemistry research》2016,25(10):2187-2204
The multi-component reaction of 2-acetylthiophene with aromatic aldehydes and either malononitrile or ethyl cyanoacetate gave the pyran derivatives 4a–4f and pyridine derivatives 5a–5f. On the other hand, the reaction of the 2-acetylthiophene with elemental sulfur and either malononitrile or ethyl cyanoacetate gave the thiophene derivatives 6a and 6b; respectively. Compounds 6a and 6b underwent a series of heterocyclic reactions to give thiazole and thiophene derivatives. All the products were assessed for antitumor activity towards human cancer human gastric cancer (NUGC and HR), human colon cancer (DLD1), human liver cancer (HA22T and HEPG2), human breast cancer (MCF), nasopharyngeal carcinoma (HONE1) cell lines. Compounds 4e, 4f, 5e, 5f, 7b, 8b, 10e, 10f, 11e, 11f, 14d-f, 15d-f, 16a,b and 18b exhibited optimal cytotoxic effect against cancer cell lines, with IC50’s in the nM range. Moreover, 7b, 10e, 14d, 15e and 16b showed no toxicity against shrimp larvae. Anti-proliferative cell activity against cancer cell lines of the most potent compounds showed that compounds 5f and 10e achieved the highest activities among the tested compounds. 相似文献
6.
Chan Kiang Lim Subramaniam Hemaroopini Shu Ying Gan Siew Mian Loo Jo Ring Low Vivien Yi Mian Jong Hsien Chuen Soo Chee Onn Leong Chun Wai Mai Chin Fei Chee 《Medicinal chemistry research》2016,25(8):1686-1694
Cancer is a leading cause of death worldwide. In our continuing search for new anticancer agents, four Malaysian Calophyllum species, namely C. castaneum, C. teysmannii, C. canum, and C. sclerophyllum, had been phytochemically studied to give compounds 1–12. All the isolated compounds were evaluated for their antiproliferative activity against nasopharyngeal (SUNE1, TW01, CNE1, HK1) and breast (HCC38, MDA-MB-231, MDA-MB-468, SKBR3) cancer cell lines via methyl thiazolyl tetrazolium cell viability assay. Among the tested compounds, isodispar B (1) showed a promising dose-dependent and a broad spectrum of cytotoxic effects on all the tested cancer cell lines; in particular, potent inhibitory activities were observed on nasopharyngeal cancer cell lines (SUNE1, TW01, CNE1, HK1), with IC50 values ranging from 3.8 to 11.5 µM. In comparison with 5-fluorouracil as positive control, compound 1 was found to exhibit at least sixfold much higher activity than the standard drug used against the nasopharyngeal cell lines. Compound 1 was later found to induce apoptotic cell death in nasopharyngeal cancer cells, as evidenced by ‘Cell Death Detection’ ELISAPLUS kit, and exhibited good cancer-specific cytotoxicity when tested with noncancerous NP460 cells. Meanwhile, compounds 2–12 displayed moderate to weak activities against the tested cancer cell lines. The findings have highlighted the therapeutic potential of compound 1 against nasopharyngeal cancer. 相似文献
7.
Shou-Bai Liu Wen-Li Mei Hui-Qin Chen Jun Wang Zhu-Nian Wang Hao-Fu Dai 《Archives of pharmacal research》2018,41(12):1170-1177
Six new compounds (1–4, 8, 10), along with six known limonoids (5–7, 9, 11, 12), were isolated from the roots of Trichilia sinensis. Their structures were elucidated on the basis of extensive spectroscopic methods including 1H NMR, 13C NMR, DEPT, HSQC, HMBC, 1H–1H COSY and ROESY experiments, as well as by comparison with the literature. All the compounds were evaluated for cytotoxicities against K562, SGC-7901 and BEL-7402 cell lines. Compounds 2, 7, 10, 11, and 12 showed weak inhibitory activity to the selected cell lines. 相似文献
8.
Ga Young Lee Byoung Ok Cho Jae Young Shin Seon Il Jang In Sook Cho Hyo Young Kim Ji Su Park Chong Woon Cho Jong Seong Kang Jang Hoon Kim Young Ho Kim 《Archives of pharmacal research》2018,41(5):490-496
Ten compounds (1–10) isolated from the seeds of Cassia tora were evaluated for tyrosinase inhibition. Compounds 3, 4, and 7 inhibited tyrosinase enzymatic activity in a dose-dependent manner, with IC50 values of 3.0?±?0.8, 7.0?±?0.4, and 9.2?±?3.4 μM, respectively. Kinetic analyses revealed a mechanism consistent with competitive inhibition. In silico molecular docking showed that compounds 3 and 4 docked in the active site of tyrosinase, whereas 7 interacted with Ala246 and Val248 at outside of the active site, and His244 and Glu256 at inside. Additionally, compounds 3, 4, and 7 suppressed melanogenesis in α-MSH-treated B16F10 melanoma cells at a concentration of 10 μM. 相似文献
9.
A series of arylidenehydrazide compounds (3a–3j) were synthesized from [6-(4-chlorophenyl)imidazo[2,1-b]thiazol-3-yl]acetic acid hydrazide. The newly synthesized compounds 3b and 3h were subjected to the National Cancer Institute’s in vitro disease-oriented antitumor screening to be evaluated for antitumor activity. Compound 3b, the most potent compound examined, displayed broad spectrum antiproliferative activity against all of the tested cell lines with log10GI50 values between ?4.41 and ?6.44. The greatest growth inhibitions were observed against an ovarian cancer cell line(OVCAR-3), a colon cancer cell line (HCT-15), two renal cancer cell lines (CAKI-1 and UO-31) and two leukemia cell lines (CCRF-CEM and SR) with log10GI10 values ?6.44, ?6.33, ?6.11, ?6.30, ?6.13 and ?6.22, respectively. Open image in new window 相似文献
10.
Ahmed Kamal Anver Basha Shaik G. Narender Reddy C. Ganesh Kumar Joveeta Joseph G. Bharath Kumar Uppula Purushotham G. Narahari Sastry 《Medicinal chemistry research》2014,23(4):2080-2092
A library of 2,5-disubstituted 1,3,4-oxadiazole derivatives of (E)-2-aryl-5-(3,4,5-trimethoxystyryl)-1,3,4-oxadiazoles 4(a–o) and (E)-2-aryl-5-(2-benzo[d][1,3]dioxol-5-yl)vinyl)-1,3,4-oxadiazoles 5(a–q) were synthesized and evaluated for their in vitro acetylcholinesterase (AChE) inhibitory activity. All the synthesized compounds exhibited moderate to good inhibitory activity toward the AChE enzyme. Among the oxadiazole derivatives examined, compounds 4a, 4g, 5c, and 5m (IC50 values of 24.89, 13.72, 37.65, and 19.63 μM, respectively) were found to be promising inhibitors of AChE. Molecular protein–ligand docking studies were examined for these compounds using GOLD docking software and their binding conformations were determined and the simultaneous interactions mode was also established for the potent derivatives. 相似文献
11.
Jean Paul Dzoyem Antoine H. L. Nkuete Barthelemy Ngameni Jacobus N. Eloff 《Archives of pharmacal research》2017,40(10):1129-1134
This study was aimed at investigating the anti-inflammatory and anticholinesterase activity of six naturally occurring flavonoids: (?) pinostrobin (1), 2′,4′-dihydroxy-3′,6′-dimethoxychalcone (2), 6-8-diprenyleriodictyol (3), isobavachalcone (4), 4-hydroxylonchocarpin (5) and 6-prenylapigenin (6). These compounds were isolated from Dorstenia and Polygonum species used traditionally to treat pain. The anti-inflammatory activity was determined by using the Griess assay and the 15-lipoxygenase inhibitory activity was determined with the ferrous oxidation-xylenol orange assay. Acetylcholinesterase inhibition was determined by the Ellman’s method. At the lowest concentration tested (3.12 µg/ml), compounds 2, 3 and 4 had significant NO inhibitory activity with 90.71, 84.65 and 79.57 % inhibition respectively compared to the positive control quercetin (67.93 %). At this concentration there was no significant cytotoxicity against macrophages with 91.67, 72.86 and 70.86 % cell viability respectively, compared to 73.1 % for quercetin. Compound 4 had the most potent lipoxygenase inhibitory activity (IC50 of 25.92 µg/ml). With the exception of (?) pinostrobin (1), all the flavonoids had selective anticholinesterase activity with IC50 values ranging between 5.93 and 8.76 µg/ml compared to the IC50 4.94 µg/ml of eserine the positive control. These results indicate that the studied flavonoids especially isobavachalcone are potential anti-inflammatory natural products that may have the potential to be developed as therapeutic agents against inflammatory conditions and even Alzheimer’s disease. 相似文献
12.
9-Amino acridine derivatives (1a–e) on condensation with dihydrofuran-2,5-dione, hexahydroisobenzofuran-1,3-dione and isochroman-1,3-dione under microwave irradiation gave corresponding condensation products 2a–e, 3a–e and 4a–e, respectively, in good yields. All these compounds were screened in vitro for anticancer activity against five human cancer cell lines, i.e., breast (T47D), lung (NCl H-522), colon (HCT-15), ovary (PA-1) and liver (Hep G2). Compounds 1-(3-methoxyacridine-9-yl) pyrrolidine-2,5-dione (2d) (ovary PA-1), 2-(2-methylacridine-9-yl)hexahydro-1H-isoindole-1,3(2H)-dione (3b) (lung NCl H-522), 2-(4-methylacridine-9-yl)hexahydro-1H-isoindole-1,3(2H)-dione (3c) (ovary PA-1), 2-(4-methoxyacridine-9-yl)hexahydro-1H-isoindole-1,3(2H)-dione (3e) (ovary PA-1) and 2-(2-methylacridine-9-yl)isoquinoline-1,3(2H,4H)-dione (4b) (ovary PA-1) exhibited IC50 values 7.1, 8.0, 5.4, 10.0 and 6.56 µM, respectively, and hence possess good anticancer activity. 相似文献
13.
Md Yousof Ali Su Hui Seong Hyun Ah Jung Susoma Jannat Jae Sue Choi 《Archives of pharmacal research》2018,41(7):753-764
In the present study, we investigated the anti-Alzheimer’s disease (AD) potential of six dihydroxanthyletin-type coumarins, 4′-hydroxy Pd–C-III (1), decursidin (2), Pd–C-I (3), 4′-methoxy Pd–C-I (4), Pd–C-II (5), and Pd–C-III (6) from Angelica decursiva by evaluating their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1). Coumarins 1–6 exhibited dose-dependent inhibition of AChE, BChE, and BACE1. IC50 values were 1.0–4.01 µM for AChE, 5.78–13.91 µM for BChE, and 1.99–17.34 µM for BACE1. Kinetic studies revealed that 1 was noncompetitive inhibitor for AChE, while 2–6 were mixed-type inhibitors of AChE. Compounds 1, 5 and 6 had mixed-type inhibitory effects against BChE; 2 was a competitive inhibitor; and 3 and 4 were noncompetitive inhibitors. Against BACE1, compounds 1, 2, 3, 5 showed mixed-type inhibition and 4, 6 were noncompetitive inhibitors. Molecular docking simulation of the compounds demonstrated negative-binding energies indicating high proximity to the active site and tight binding to the enzyme. These data suggested that the compounds inhibited AChE, BChE, and BACE1, providing a preventive and therapeutic strategy for AD treatment. 相似文献
14.
A. F. M. Motiur Rahman Yang Lu Hwa-Jong Lee Hyunji Jo Wencui Yin Mohammad Sayed Alam Hyochang Cha Adnan A. Kadi Youngjoo Kwon Yurngdong Jahng 《Archives of pharmacal research》2018,41(12):1131-1148
In efforts to develop effective anticancer therapeutics with greater selectivity toward cancerous cell and reduced side-effects, such as emetic effects due to detrimental action of the drug toward the intestinal flora, a series of linear diarylheptanoids (LDHs) were designed and synthesized in 7 steps with good-to-moderate yields. All synthesized compounds were evaluated for their antibacterial, antiproliferative, and topoisomerase-I and -IIα inhibitory activity. Overall, all compounds showed little to no activity against the bacterial strains tested. Most of the synthesized compounds showed good antiproliferative activity against human breast cancer cell lines (T47D); specifically, the IC50 values of compounds 6a, 6d, 7j, and 7e were 0.09, 0.64, 0.67, and 0.99 μM, respectively. Among the tested compounds, 7b inhibited topo-I by 9.3% (camptothecin 68.8%), 7e and 7h inhibited topo-IIα by 38.4 and 47.4% (etoposide 76.9%), respectively, at the concentration of 100 μM. These results suggest that a set of promising anticancer agents can be obtained by reducing inhibitory actions on different microbes to provide enhanced selectivity against cancerous cells. 相似文献
15.
Hyun Ji Kim Hye Mi Kim Byeol Ryu Woo-Seok Lee Ji-Sun Shin Kyung-Tae Lee Dae Sik Jang 《Archives of pharmacal research》2016,39(2):231-239
Fourteen compounds, coumarin (1), demethylsuberosin (2), xanthotoxin (3), psoralen (4), decursinol (5), decursin (6), decursinol angelate (7), chikusetsusaponin IVa (8), chikusetsusaponin IVa methyl ester (9), ethyl caffeate (10), syringaresinol (11), cnidilide (12), farnesol (13), and linoleic acid (14), were isolated from phytopharmaceutical PG201 (Layla®) by activity-guided fractionation utilizing inhibitory activity on nitric oxide (NO) production in vitro. The isolates 1–14 were evaluated for their inhibitory activity on LPS-induced NO and prostaglandin E2 (PGE2) productions in RAW 264.7 cells. All the compounds except 14 displayed suppressive effects on LPS-induced NO and PGE2 production with IC50 values ranging from 8 to 60 μM. Among these, compound 10 showed the most potent inhibitory effect on NO production from RAW 264.7 cells with an IC50 value of 8.25 μM. Compounds 2, 9, and 10 exhibited high inhibitory effects on PGE2 production with the IC50 values of 9.42, 7.51, and 6.49 μM, respectively. These findings suggest that compounds 2, 9, and 10 are the potential anti-inflammatory active constituents of PG201 and further study may be needed to explain their mechanism of action. 相似文献
16.
Jiah Lim Yoojin Song Jung-Hee Jang Chul-Ho Jeong Sooyeun Lee Byoungduck Park Young Ho Seo 《Archives of pharmacal research》2018,41(10):967-976
Aspirin is one of the oldest drugs for the treatment of inflammation, fever, and pain. It is reported to covalently modify COX-2 enzyme by acetylating a serine amino acid residue. By virtue of aspirin’s acetylating potential, we for the first time developed novel acetyl-donating HDAC inhibitors. In this study, we report the design, synthesis, in silico docking study, and biological evaluation of acetyl-donating HDAC inhibitors. The exposure of MDA-MB-231 cells with compound 4c significantly promotes the acetylation of α-tubulin and histone H3, which are substrates of HDAC6 and HDAC1, respectively. In silico docking simulation also indicates that compound 4c tightly binds to the deep substrate-binding pocket of HDAC6 by coordinating the active zinc ion in a bidentate manner and forming hydrogen bond interactions with Ser531 and His573 amino acid residues. In particular, compound 4c (GI50?=?147 μM) affords the significant enhancement of anti-proliferative effect on MDA-MB-231 cells, compared with its parent compound 2c (GI50?>?1000 μM) and acetyl-donating group deficient compound 6 (GI50?=?554 μM). Overall, compound 4c presents a novel strategy for developing acetyl-donating HDAC inhibitors. 相似文献
17.
Swapna Sundaree Buchi Reddy Vaddula Mukund P. Tantak Santosh B. Khandagale Chun Shi Kavita Shah Dalip Kumar 《Medicinal chemistry research》2016,25(5):941-950
A series of N′-((1-(substituted)-1H-indol-3-yl)methylene)hydrazides were synthesized and evaluated for their in vitro antiproliferative activities against various cancer cell lines. Formation of indole hydrazide–hydrazones was accomplished by the reaction of indole 3-carboxaldehyde with aryl/alkyl hydrazides in the presence of acetic acid. Out of synthesized twenty-two compounds, some of the analogs exhibited specificity toward breast (18b, 18d, 18f and 18j) and prostate (18t and 18v) cancer cells. Among the prepared derivatives, compounds 18b, 18d and 18j were most cytotoxic (IC50 = 0.9, 0.4 and 0.8 µM, respectively) against the screened cancer cell lines. Exposure of PC3 cells to either 18d or 18j resulted in increased levels of cleaved PARP1, indicating that indolyl hydrazide–hydrazones induce apoptosis in PC3 cells. 相似文献
18.
Dongamanti Ashok Devulapally Mohan Gandhi Aamate Vikas Kumar Gundu Srinivas Malladi Srinivas Reddy Sivan Sree Kanth Manga Vijjulatha 《Medicinal chemistry research》2016,25(12):2882-2894
A series of novel chroman scaffold incorporate spirochromanone derivatives were synthesized from 2-hydroxyacetophenone and cyclic alkanones under microwave irradiation in good yields. Newly synthesized compounds were characterized by analytical and spectral (IR, proton nuclear magnetic resonance, 13C nuclear magnetic resonance, and mass spectrometry) methods. The synthesized compounds were evaluated for their antioxidant and anti-inflammatory activities and were compared with standard drugs. Among all the synthesized compounds 3d (6.09), 3g (5.32), 3h (2.03), 4a (1.17), 4b (0.50), 4c (6.59), 4d (7.86), 4e (6.85), 4f (4.82), and 4g (6.59) were exhibited higher antioxidant activity comparable to that of ascorbic acid (IC50 8.64?µM). The compounds 3a, 3b, 3c, 4c, and 4d were found to have good anti-inflammatory activity. The binding mode of the titled compounds has been proposed based on the molecular docking studies. 相似文献
19.
Le Duc Dat Nguyen Phuong Thao Bui Thi Thuy Luyen Bui Huu Tai Mi Hee Woo Zahid Manzoor Irshad Ali Young Sang Koh Young Ho Kim 《Archives of pharmacal research》2017,40(3):311-317
Twelve saponins were isolated from the leaves of Acanthopanax koreanum, including one new lupane-type triterpene glycoside, named acankoreoside R (1), together with 11 known triterpenoid saponins (2–12). Their structures were elucidated by 1D and 2D nuclear magnetic resonance (NMR), mass spectroscopic data (MS). All of the fractions and isolated saponins were evaluated for anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) by ELISA. Among them, compounds 1–5, 7, 10, and 12 showed strong inhibitions towards interleukin-12 (IL-12) production with IC50 values ranging from 1.59 to 5.46 µM. Other compounds were weak or inactive toward IL-12 p40 production. 相似文献
20.
Frans J. Smit Jaco J. Bezuidenhout Carlos C. Bezuidenhout David D. N’Da 《Medicinal chemistry research》2016,25(4):568-584
A series of aminoferrocenyl–chalcone amides 11–19 were synthesized through condensation of a carboxylic acid-functionalized chalcone 10 with ferrocenylamines, using 1,1′-carbonyldiimidazole as the coupling agent. The compounds were screened for their antiplasmodial activities against CQS 3D7 and CQR FCR3 strains of Plasmodium falciparum. All compounds were found to be active, with IC50 values ranging between 0.5–4.5 and 2.1–6.6 µM against 3D7 and FCR3, respectively. Amide 11, featuring a 2-aminoethylene linker, was the most active of all, with IC50 values of 2.6 and 2.1 µM against the 3D7 and FCR3 strains, respectively. In screens against a panel of three cancer cell lines, i.e., TK-10, UACC-62, and MCF-7, amide 19, with a piperazinyl linker, showed increased activity against all three cell lines, compared to the reference drug, parthenolide. Antimicrobial assays that had been performed on six different microorganisms revealed that most of the synthesized amides were inactive against all of these microorganisms. Compound 17, however, with an aminodi(ethyleneoxy) linker, displayed moderate bactericidal activity against the gram-negative microorganisms, with a MIC100 value of 128 µM. The outcomes of this study may hence significantly contribute toward malaria and cancer chemotherapy research, and more generally to the growing body of research that aims at illustrating the potential of employing organometallic compounds in medicinal chemistry programs. 相似文献