Design,synthesis, crystal structures and biological evaluation of some 1,3-thiazolidin-4-ones as dual CDK2/EGFR potent inhibitors with potential apoptotic antiproliferative effects

A series of novel thiazolidine-4-one derivatives was synthesized by reacting 1,4-disubstituted hydrazine carbothioamides with diethyl azodicarboxylate. The structures were confirmed by spectroscopic data as well as single-crystal X-ray analyses. The antiproliferative activity of the synthesized compounds was investigated against four human cancer cell lines using an MTT assay. Compounds 5d, 5e, and 5f revealed the most potent antiproliferative activity with GI₅₀ values ranging from 0.70 µM to 1.20 µM, compared to doxorubicin GI₅₀ value = 1.10 µM. Compounds 5d, 5e, and 5f were further investigated for their inhibitory activities against CDK2 and EGFR as potential targets for their molecular mechanism. Compounds 5e and 5f have showed potent inhibitory activity to CDK2 enzyme with IC₅₀ values of 18 and 14 nM, which is more potent than the reference dinaciclib (IC₅₀ = 20 nM). Moreover, compounds 5e and 5f were the most potent EGFR inhibitors, with IC₅₀ values of 93 and 87 nM, respectively, compared to the reference erlotinib (IC₅₀ = 70 nM). In addition, the most potent derivatives were tested for their apoptotic activity against caspases 3, 8, and 9, and the results showed that compounds 5d, 5e, and 5f revealed a greater increase in active caspases 3,8 and 9 than doxorubicin. Also, compounds 5d, 5e, and 5f elevated cytochrome C levels in the MCF-7 human breast cancer cell line by about 15.5, 15.8, and 16.5 times, respectively. Finally, a molecular docking study was performed to investigate the binding sites of these compounds within the active sites of CDK2 and EGFR targets, and the results confirmed that the most potent CDK2 and EGFR inhibitor 5h also have showed the highest docking score.     

Synthesis and in vitro activity of a non-epimerizable analog of the angiotensin-converting enzyme inhibitor A58365A

The 3-methyl-substituted analog (±)-3 of the angiotensin converting enzyme inhibitor A58365A (1) was synthesized from lactone 4 and amino acid ester 16, via key intermediates 18, 19 and 21a,b. Compound (±)-3 was found to possess powerful ACE inhibitory activity (IC₅₀ = ca 500 nM), as judged by in vitro tests against porcine kidney ACE, under conditions in which the commercial drug captopril has IC₅₀ = 280 nM.     

Design,synthesis and docking studies of new hydrazinyl-thiazole derivatives as anticancer and antimicrobial agents

Increase in the number of infections caused by pathogenic microbes in cancer patients has prompted the searcher to invest in the development of agents having dual anticancer and antimicrobial properties. The present study is concerned with synthesis and screening for anticancer and antimicrobial activity of a series of 5-hydrazinyl-2-(2-(1-(thien-2-yl)ethylidene)hydrazinyl)thiazole derivatives. The structure elucidation of the synthesized hydrazinyl thiazole derivatives was illustrated by spectroscopic and elemental analysis. All the newly synthesized compounds 5a-p were evaluated for in-vitro cytotoxic activity against breast carcinoma (MCF-7 cell line), hepatocellular carcinoma (HePG-2) and colorectal cancer (HCT-116) cell lines using MTT assay method. Compounds 5 g, 5h showed broad spectrum activity against three cancer cell lines with IC₅₀ ranged from 3.81 to 11.34 µM in compared to the reference drug Roscovitine (IC₅₀ = 9.32 to 13.82 µM), while compounds 5 l and 5 m were found to be more selective against HePG-2 and HCT-116 cell line (IC₅₀ = 9.29 and 8.93 µM respectively) and compound 5j was more selective against HePG-2 and MCF-7 cell lines (IC₅₀ = 6.73 and 10.87 µM respectively). The inhibitory activity of the most promising compounds was tested against the EGFR and ARO enzymes and were further tested for apoptosis and Annexin V/PI staining. The results of enzyme-based tests revealed that the tested compound 5j has a dual inhibitory effect on the EGFR and ARO enzymes with IC₅₀ = 82.8 and 98.6 nM respectively in compared to the reference drugs Erlotinib and Letrozole (IC₅₀ = 62.4 and 79 nM respectively). Furthermore, the majority of the tested hydrazinyl thiazole derivatives exhibited significant antimicrobial activity against the used pathogenic microbes species. Compounds 4b, 5h, 5j and 5 m exerted a good antibacterial and antifungal activity against all tested pathogenic microbes. Therefore, it was concluded that compounds 5 h, 5j and 5 m proved to possess dual anticancer and antimicrobial agent and may serves as a useful lead compounds in search for further modification or derivatization to give more potent and selective agents.     

Design,synthesis, antimicrobial evaluations and in silico studies of novel pyrazol-5(4H)-one and 1H-pyrazol-5-ol derivatives

A new series of 1,4-disubstituted 3-methylpyrazol-5(4H)-one derivatives were synthesized by reacting various substituted aromatic aldehydes with 3-methylpyrazol-5(4H)-one derivatives through Knoevenagel condensation by conventional as well as by exposure to microwave irradiations. After that newly synthesized compounds of 1,4-disubstituted 3-methyl-1H-pyrazol-5-ol were prepared from these derivatives by reduction reaction of sodium borohydride at 0–5 °C. Sixty-four heterocyclic compounds containing a pyrazole moiety were synthesized with good to excellent yields (51 to 91%). Compounds (3d, 3m, 4a, 4b, 4d, and 4g) showed potent antibacterial activity against MSSA (Methicillin-susceptible strains of Staphylococcus aureus) and MRSA (Methicillin-resistant strains of Staphylococcus aureus) with MIC (the minimum inhibitory concentration) ranging between 4 and 16 µg/mL as compared to ciprofloxacin (MIC = 8–16 µg/mL). Compounds (4a, 4h, 4i, and 4l) showed potent antifungal activity against Aspergillus niger with MIC ranging between 16 and 32 µg/mL as compared to fluconazole (MIC = 128 µg/mL). In particular, compound 4a exhibited the strongest activity among the synthesized compounds in both bacterial and fungal strains with MIC ranging between 4 and 16 µg/mL. Furthermore, the nine most active compounds showed a good ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile in comparison to ciprofloxacin and fluconazole as reference drugs. Molecular docking predicted that DHFR (dihydrofolate reductase) protein from Staphylococcus aureus and NMT (N-myristoyl transferase) protein from Candida albicans are the most suitable targets for the antimicrobial activities of these potent compounds.     

Synthesis of some analogues of nucleoside 5′-triphosphates

Reaction of propane -1,3- disulphonyl chloride with the appropriate 5' - amino - 5'.- deoxyribonucleoside gave 5' - deoxy -5′-(3- sulphopropanesulpho5' - Deoxy - 5' - p- sulphaminobenzenesulphonylaminothymidine (8) was obtained by treatment of 5' - p- aminobenzenesulphonylamino - 5' -deoxythymidine (10) with SO₃,-triethylamine. This reaction gave also some 5'-p- aminobenzenesulphonylamino - 5' - deoxy - 3' - O - sulphothymidine (12). Compounds 2 and 3 were inactive when tested for inhibitory activity against E.coli RNA polymerase holoenzyme. Compounds 1 and 8 inhibited E.coli DNA polymerase I non-competitively at relatively high concentrations. Compound 4 was without significant inhibitory activity against HSV-1 DNA polymerase.     

Qingqianliusus A-N, 3,4-seco-dammarane triterpenoids from the leaves of Cyclocarya paliurus and their biological activities

Fourteen previously unreported 3,4-seco-dammarane triterpenoids named Qingqianliusus A-N (1–14), along with four known 3,4-seco-dammarane triterpenoid derivatives (15–18) were isolated from the 95 % ethanol extract of the Cyclocarya paliurus leaves. Compounds 1 and 2 possess a rare 3,11-heptacyclic lactone as natural product, and several pairs of the 3,4-seco-dammarane triterpenoid epimers with R/S configuration at C-24 were investigated and determined in detail for the first time. Compounds 8, 11, and 14 showed good α-glucosidase inhibitory effects with IC₅₀ values of 4.97 ± 0.63, 7.08 ± 0.53, and 3.76 ± 0.77 μM, respectively. Meanwhile, compound 11 was also found potent inhibition rate of 35.83 % against COX-2, as compared with the positive control celecoxib (70.28 %). In addition, compounds 3, 7, 10, and 13 exhibited outstanding cytotoxicities against human gastric cancer cell lines (BGC-823) with IC₅₀ values of 7.69 ± 0.21, 8.47 ± 0.41, 9.04 ± 0.61, and 8.86 ± 0.38 μM, respectively. Compounds 13 and 3 had modest activities on human colon cancer cell lines (HCT-116) with IC₅₀ values of 8.80 ± 0.36 and 9.45 ± 0.93 μM, respectively.     

Facile Synthesis,Antimicrobial Activity and Molecular Docking of Novel 2,4,5‐Trisubstituted‐1H‐Imidazole–Triazole Hybrid Compounds

In the present work, a series of 18 imidazole–triazole hybrids ( 4a–r ) has been synthesized in good yield from substituted naphthaldehydes and 1,2‐diketones in the presence of ammonium acetate. The synthesized imidazole–triazole hybrid compounds were characterized by spectral techniques and screened in vitro for their antimicrobial activity. Compound 4h was found to be most active against Staphylococcus epidermidis, and compound 4e exhibited promising activity against Escherichia coli. In the fungal species under test, compound 4q was most potent against Aspergillus niger, even better than the fluconazole. Further, compound 4e was docked in the binding site of DNA gyrase topoisomerase II of E. coli.     

Diazenyl schiff bases: Synthesis,spectral analysis,antimicrobial studies and cytotoxic activity on human colorectal carcinoma cell line (HCT-116)

A series of diazenyl schiff bases have been synthesized by reaction of salicylaldehyde containing azo dyes with various substituted aniline derivatives in the presence of acetic acid as catalyst. The structures of diazenyl derivatives were determined by FTIR, UV–vis, ¹H NMR, ¹³C NMR, CHN analysis, fluorimetric and mass spectroscopic studies. The synthesized derivatives were screened for their in vitro antimicrobial activity against various Gram-positive (S. aureus, B. subtilis, B. cereus), Gram-negative (S. typhi, S. enterica, E. coli, P. aeruginosa) bacterial and fungal (C. albicans, A. niger and A. fumigatus) strains, using cefadroxil (antibacterial) and fluconazole (antifungal) as standard drugs. The diazenyl schiff bases were also screened for their cytotoxicity against human colorectal carcinoma cell line (HCT-116) using 5-fluorouracil as standard drug by Sulforhodamine-B Stain (SRB) assay. The schiff bases exhibited significant activity toward both Gram-positive, Gram-negative bacterial and fungal strains. Most of the synthesized derivatives showed high activity against S. enterica. 4-((2,5-Dichlorophenyl)diazenyl)-2-((3-bromophenylimino)methyl)phenol (SBN-40) was found to be very active against S. aureus, B. cereus and E. coli, with MIC = 0.69 (µM/ml × 10²). The compound 4-((2-bromophenyl)diazenyl)-2-((4-nitrophenylimino)methyl)phenol (SBN-13) possessed comparable activity (IC₅₀ = 7.5 µg/ml) to the standard drug 5-fluorouracil (IC₅₀ = 3.0 µg/ml) against human colorectal carcinoma cell line (HCT-116).     

Anticancer and antimicrobial evaluation of newly synthesized steroidal 5,6 fused benzothiazines

A series of new 5α-cholestano [5,6-b] benzothiazines (4–6) has been synthesized by the reaction of 5α-cholestan-6-one (1–3) with 2-aminothiophenol in the presence of iodine. The structures of newly synthesized compounds have been established on the basis of spectral and analytical data. Compounds (1–6) were screened for in vitro anticancer activity against the human cancer cell lines; SW480 (colon adenocarcinoma cells), A549 (lung carcinoma cells), HepG2 (hepatic carcinoma cells) and HeLa (cervical cancer cells) using MTT assay during which the products (4–6) showed marked increase in anticancer activity and in particular, compound 6 showed IC₅₀ = 13.73 μmol L⁻¹ against HeLa cells, being more effective than Doxorubicin against the same cells. Compounds 4 and 6 also showed minimum IC₅₀ of 15.83 μmol L⁻¹ and 16.89 μmol L⁻¹ against HepG2 and A549 cells, respectively. Compounds (1–6) were also tested for in vitro antimicrobial activity against different bacterial as well as fungal strains during which newly synthesized compounds (4–6) were found more potent than starting compounds (1–3). Compound 4 was found to be more potent than the reference drug, Chloramphenicol, in the case of Escherichia coli while compound 5 was found almost equally potential antifungal agent against P. marneffei in comparison with the reference drug, Nystatin.     

Arylnaphthalide lignans from Saussurea medusa and their anti-inflammatory activities

Five new arylnaphthalide lignans (1 ? 4a/4b), together with five known analogues (5–9), were isolated from whole plants of Saussurea medusa. Compound 4 was characterized as an aryltetralin lignan with an unusual C-7′-C-9 oxygen bridge group, and a chiral HPLC analysis was carried out to afford one pair of enantiomers (4a/4b). Structures of the new compounds were elucidated by extensive spectroscopic and electronic circular dichroism (ECD) calculations. All compounds were firstly isolated from S. medusa, and compounds 1–5, 7 and 8 had never been obtained from the genus Saussurea previously. Furthermore, this is the first report of arylnaphthalide lignans isolated from S. medusa. anti-inflammatory activities of the compounds were evaluated by determining their inhibitory activities on the production of NO by LPS-stimulated RAW 264.7 cells. Compounds (?)-4a and 5 exerted the significant inhibition activities with IC₅₀ values of 13.4 ± 1.5 and 15.7 ± 1.1 μM, respectively, which even exceeded the positive control quercetin (IC₅₀ = 15.9 ± 1.2 μM). Compounds 2, (+)-4b, 6 and 9 exhibited moderate inhibitory activities with IC₅₀ values ranging from 19.7 ± 1.9 to 47.4 ± 3.1 μM. Further analysis by molecular docking showed that almost all the active compounds could interact with the amino acid residues of iNOS proteins, which also supported their anti-inflammatory activities.     

Cyclopeptides and polyketides from coral-associated fungus, Aspergillus versicolor LCJ-5-4

Three new cyclopentapeptides, versicoloritides A-C (1-3), a new orcinol tetramer, tetraorcinol A (4), and two new lactones, versicolactones A and B (5 and 6) together with three known metabolites, diorcinol, glyantrypine, and cordyol C were isolated from the fermentation broth of the coral-associated fungus Aspergillus versicolor LCJ-5-4. Their structures were elucidated by spectroscopic and chemical methods. The new compounds 1-4 were evaluated for their radical-scavenging activity and antimicrobial activity against Staphylococcus aureus, Escherichia coli, Enterobacter aerogenes, Bacillus subtilis, Pseudomonas aeruginosa, and Candida albicans and cytotoxicity against P388 and Hela cell lines. Compound 4 showed weak radical-scavenging activity against the DPPH radical with an IC₅₀ value of 67 μM.     

Synthesis of novel 2,3‐disubstituted quinazolin‐4(3H)‐one derivatives containing hydrazone skeleton as potent urease inhibitors and their antimicrobial activities

A new series of quinazolinones containing hydrazone moiety were synthesized, and their inhibitory activities on urease were assessed in vitro. Most of the compounds exhibited potent urease inhibitory activity. Among the synthesized compounds, molecule 4a bearing furan ring has the best inhibitory effect against urease with IC₅₀ = 2.90 ± 0.11 μg/mL. Compounds 4f , 4g , 4h , 4i , and 4j have hydroxy group on phenyl ring. Compound 4i is the most active inhibitor among these compounds with IC₅₀ = 5.01 ± 0.10 μg/mL, which has 3‐Cl and 4‐Br on phenyl ring. Also, newly synthesized compounds had been tested for their antimicrobial effects against three of Gram‐positive bacteria (Bacillus cereus 702 Roma, Staphylococcus aureus ATCC 25923, and Streptococcus pyogenes ATCC 19615) and three of Gram‐negative bacteria (Escherichia coli ATCC 25922, Proteus vulgaris ATCC 13315, and Pseudomonas aeruginosa ATCC 27853). Antimicrobial activity results show that compounds 4a , 4h , 4j , 4f , and 4l have the lowest minimum inhibitory concentration (MIC) value of 1000 μg/mL to all tested bacteria. The other compounds have the MIC value of >1000 μg/mL to all tested bacteria.     

Identification of Antibacterial Metabolites from Endophytic Fungus Aspergillus fumigatus,Isolated from Albizia lucidior Leaves (Fabaceae), Utilizing Metabolomic and Molecular Docking Techniques

The rapid spread of bacterial infection caused by Staphylococcus aureus has become a problem to public health despite the presence of past trials devoted to controlling the infection. Thus, the current study aimed to explore the chemical composition of the extract of endophytic fungus Aspergillus fumigatus, isolated from Albizia lucidior leaves, and investigate the antimicrobial activity of isolated metabolites and their probable mode of actions. The chemical investigation of the fungal extract via UPLC/MS/MS led to the identification of at least forty-two metabolites, as well as the isolation and complete characterization of eight reported metabolites. The antibacterial activities of isolated metabolites were assessed against S. aureus using agar disc diffusion and microplate dilution methods. Compounds ergosterol, helvolic acid and monomethyl sulochrin-4-sulphate showed minimal inhibitory concentration (MIC) values of 15.63, 1.95 and 3.90 µg/mL, respectively, compared to ciprofloxacin. We also report the inhibitory activity of the fungal extract on DNA gyrase and topoisomerase IV, which led us to perform molecular docking using the three most active compounds isolated from the extract against both enzymes. These active compounds had the required structural features for S. aureus DNA gyrase and topoisomerase IV inhibition, evidenced via molecular docking.     

Multistep synthesis and screening of heterocyclic tetrads containing furan,pyrazoline, thiazole and triazole (or oxadiazole) as antimicrobial and anticancer agents

In the present study novel heterocyclic tetrads containing furan, pyrazoline, thiazole and triazole (or oxadiazole) (1, 2, 3, 4a-e and 5a-e) were designed and synthesized and investigated for their antimicrobial (against selected bacteria and fungi) and anticancer potential. The molecules 4e and 5e containing 4-fluoro phenyl and 4-fluoro benzyl substituents showed promising antimicrobial (antibacterial and antifungal activities with MICs ranging between 0.5 and 8 µg/mL. Compounds 3 exhibited potent anticancer activity with an IC₅₀ value of 0.49 ± 1.45 µM against the human gastric cancer cell line (BGC-823) whereas compound 4e displayed an IC₅₀ value of 0.65 ± 0.53 µM against breast cancer (MCF-7) cell line respectively. All compounds showed selective toxicity against the cancer cell lines compared to human normal liver cell lines. Molecular docking studies of the most potent compounds (3 and 4e) against selected microbial and cancer proteins revealed the crucial binding interactions of the potent compounds with the target enzymes. Compounds 3 and 4e are promising lead molecules to be developed as potential drug candidates.     

Synthesis of thiazole clubbed pyrazole derivatives as apoptosis inducers and anti-infective agents

Fourteen N-[{(substituted-phenylthiazol-2-yl)-3-aryl-1H-pyrazol-4-yl}methylene]-5-substituted-thiazol-2-amine (5a-n) analogs were synthesized by the reaction of 3-aryl-1-(thiazol-2-yl)-1H-pyrazole-4-carbaldehyde and substituted thiazole amines. The structures of prepared compounds were delineated by elemental analysis, FT-IR and ¹H NMR spectra. These analogs were scrutinized for in vitro anti-infective and cytotoxic activities. Some thaizole clubbed pyrazole derivatives were assessed for their cytological changes in germ cells of Capra hircus by using histomorphological analysis, fluorescence assay and apoptosis quantification. Compound 5l having 4-NO₂ substituent induced the significant apoptosis in tested cells of Capra hircus. The results revealed that compounds 5c, 5e, 5k, and 5l have commendable antibacterial activity within MIC range of 62.5–250 μg/ml. Compound 5c emerged as a potent antimalarial compound by exhibiting IC₅₀ value of 0.23 μg/ml and compound 5j induced paralysis of Pherentima posthuma at 8.6 ± 1.94 min and death at 20 ± 5.04 min, respectively. Compound 5j revealed an excellent cytotoxicity at IC₅₀ value of 30.7 and < 10 μg/ml against MCF-7 and HeLa cells, respectively. Individually, compounds 5c, 5j and 5l could be considered as promising anti-infective and cytotoxic compounds.     

Synthesis of new 1,2-disubstituted benzimidazole analogs as potent inhibitors of β-Glucuronidase and in silico study

New benzimidazole analogues (1–18) were synthesized and characterized through different spectroscopic techniques such as ¹H NMR, ¹³C NMR and HREI-MS. All analogues were screened for β-glucuronidase inhibitory potential. All analogues showed varied degree of inhibitory potentials with IC₅₀ values ranging between 1.10 ± 0.10 to 39.60 ± 0.70 μM when compared with standard _D-saccharic acid-1,4- lactone having IC₅₀ value 48.30 μM. Analogues 17, 11, 9, 6, 1 and 13 having IC₅₀ values 1.10 ± 0.10, 1.70 ± 0.10, 2.30 ± 0.10, 5.30 ± 0.20, 6.20 ± 0.20 and 8.10 ± 0.20 μM respectively, showed excellent β-glucuronidase inhibitory potential many folds better than the standard. All other analogues also showed good inhibitory potential better as compared to standard. Structure activity relationships (SAR) has been established for all compounds. The results from molecular docking studies supports the established SAR and developed a strong correlation with the results from in to vitro assay. The molecular docking results clearly highlighted how substituents like nitro and chloro affect the binding position of the active compounds in the active site. The docking results were also used to properly establish the effect of bulky substituents of least active compounds on reduced β-glucuronidase inhibitory activity. Compounds 1–18 were found non-toxic.     

Comparative evaluation of antibacterial potentials of nano cobalt oxide with standard antimicrobials

Development of suitable potent antimicrobial is the urgent need of modern era to cope up the problem of antimicrobial resistance. The applications of nanotechnology in metal oxides have shown favorable effects to some extent in this area. Thus, the present study was investigated to evaluate the antibacterial properties of cobalt oxide (Co₃O₄) nanoparticles at different concentrations and their comparison with standard antimicrobials i.e. tetracycline and gentamicin. Nanoparticles were synthesized and characterized by standard techniques. The antibacterial potentials of Co₃O₄ nanoparticles against S. aureus and E. coli were determined at various concentrations. The maximum zone of inhibitions of Co₃O₄ nanoparticles against S. aureus and E. coli at 500 μg/ml were 21.17 mm and 24.00 mm, respectively. The Co₃O₄ nanoparticles seemed more effective than gentamicin against S. aureus and E. coli. The nanoparticles with respect to tetracycline showed higher than 1 activity index at ≥ 125 μg/ml for E. coli and ≥31.25 μg/ml for S. aureus. It was also higher than 1 at all compared concentrations with respect to gentamicin against both bacteria. In conclusion, Co₃O₄ nanoparticles seemed to have potent antibacterial potential and these might be very helpful to replace the conventional antimicrobials to solve the problem of antibacterial resistance.     

Two new sesquiterpenes and six norsesquiterpenes from the solid culture of the edible mushroom Flammulina velutipes

One new sesquiterpene with a novel carbon skeleton, flammulinol A (1), one new isolactarane sesquiterpene and six isolactarane-related norsesquiterpenes, flammulinolides A–G (2–8), as well as sterpuric acid, were isolated from the solid culture of Flammulina velutipes. The structures of the new compounds were elucidated by spectroscopic methods. The absolute configuration of C-3 in 1 was determined via the circular dichroism data analysis based on the octane rule of cyclopentenone, whereas the absolute configurations of compounds 2, and 5–8 were assigned using the circular dichroism data of the [Rh₂(OCOCF₃)₄] complex. Compounds 2, 3, and 7 showed strong cytotoxicity against KB cell line with the IC₅₀ of 3.9, 3.6, and 4.7 μM, respectively. Compound 4 showed strong cytotoxicity against Hela cell line with the IC₅₀ of 3.0 μM. The plausible biosynthetic pathway for 2–9 in F. velutipes was discussed.     

Euphorane C,an unusual C17-norabietane diterpenoid from Euphorbia dracunculoides induces cell cycle arrest and apoptosis in human leukemia K562 cells

Four new polycyclic diterpenoids euphoranes A ? D (1–4), together with 12 known terpenoids (5–16) were isolated from the whole plants of Euphorbia dracunculoides. Compound 2 represents the first example of aromatic 15,16,17-trinorabietane diterpenoid in Euphorbia species, and euphorane C (3) is an unusual 17-norabietane diterpenoid. The absolute configurations of 1, 2, and 4 were determined by single crystal X-ray diffraction, while that of 3 was established with the aid of ECD and 1D NMR quantum chemical calculation. Moreover, the absolute stereochemistry of 11 was demonstrated for the first time by crystallographic data. Compounds 1–16 were screened for antiproliferative activities against five human cancer cell lines, and 3 showed significant cytotoxicity against the human leukemia K562 cells with IC₅₀ value of 3.59 μM. Preliminary mechanistic investigation revealed that 3 could induce cell cycle arrest at G0/G1 phase and apoptosis in K562 cells.