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Guided by Global Natural Products Social molecular networking, two p-terphenyl derivatives and one 4,5-diphenyl-2-pyrone analogue, peniterphenyls A-C (1-3), together with five known p-terphenyl derivatives (4-8) and sulochrin (9), were obtained from a deep-sea-derived Penicillium sp. SCSIO41030. Their structures were elucidated using extensive NMR spectroscopic and HRESIMS data and by comparing the information with literature data. Peniterphenyl B (2) represented the first reported natural product possessing a 4,5-diphenyl-substituted 2-pyrone derivative. The p-terphenyl derivatives displayed inhibitory activities against HSV-1/2 with EC50 values ranging from 1.4 ± 0.6 to 9.3 ± 3.7 μM in Vero cells, which showed that they possessed antiviral activities with low cytotoxicity, superior to the current clinical drug acyclovir (EC50 3.6 ± 0.7 μM). Peniterphenyl A (1) inhibited HSV-1/2 virus entry into cells and may block HSV-1/2 infection through direct interaction with virus envelope glycoprotein D to interfere with virus adsorption and membrane fusion, and thus differs from the nucleoside analogues such as acyclovir. Our study indicated peniterphenyl A (1) could be a promising lead compound against HSV-1/2.

One new citrinin monomer derivative (1), and two new natural products α-pyrone analogues (2a and 2b), were isolated from the sponge derived fungus Penicillium sp. SCSIO 41302. Their structures were determined by extensive spectroscopic analysis, chiral-phase HPLC analysis, modified Mosher's method, ECD calculations, and X-ray single-crystal diffraction. Bioactivity screening showed that compounds 2b and 8 exhibited obvious inhibitory activities against pancreatic lipase and acetyl cholinesterase with IC50 values of 48.5 and 4.8 μM, respectively, which indicated that different chiral center between enantiomers (2a and 2b) might result in different biological activities (IC50 value against PL for 2a >100 μg/ml).

A new glyoxylate-containing benzene derivative, methyl 2-(4-hydroxy-3-(3'-methyl-2'-butenyl)phenyl)-2-oxoacetate (1), together with ten known compounds (2-11), were isolated from the marine algicolous fungus, Aspergillus sp. SCSIO 41304. Their planar structures and absolute configurations were elucidated by detailed NMR, MS spectroscopic analysis and comparing with literature data. Compound 1 was isolated as a new fungal secondary metabolite, possessing a methyl glyoxylate moiety R-CO-CO-OCH3, which is rare in natural sources. All the isolated compounds (1-11) were tested for their antibacterial and enzyme inhibitory activities against acetylcholinesterase (AChE) and pancreatic lipase (PL). Among these compounds, aspulvinone H (4) showed moderate inhibition against AChE and PL with IC50 values of 25.95 and 47.06 μM, respectively. Further molecular docking simulation exhibited that compound 4 could well bind to the catalytic pockets of the AChE and PL.

In devotion to investigating structurally novel and biologically active marine natural products, a dimer of a zinc complex, dizinchydroxyneoaspergillin (1), aspernones A-E (2-6), five cyclopentenone derivatives together with known polyketides (7-10), and neoaspergillic acid analogues (11-14) were isolated from the sponge-associated fungus Aspergillus ochraceopetaliformis SCSIO 41018. Their structures were elucidated on the basis of spectroscopic analysis, electronic circular dichroism (ECD) analysis, and X-ray diffraction. Dizinchydroxyneoaspergillin (1) displayed significant bactericide effects toward methicillin-resistant Staphyloccocus aureus, Staphyloccocus aureus, Enterococcus faecalis, Acinetobacter baumannii, and Klebsiella pneumonia with MIC values of 0.45-7.8 μg/mL and moderate in vitro cytotoxic activities against the K562, BEL-7402, and SGC-7901 cell lines with IC50 values of 12.88 ± 0.14, 15.83 ± 0.23, and 15.08 ± 0.62 μM, respectively. This is the first time to report the dimer of the zinc complex of hydroxyneoaspergillic acid conjunction at Zn-N-4 by a coordination bond. Additionally, compound 1 displayed significant antibacterial and cytotoxic activities, which would be a promising drug lead and could attract much attention from both chemists and pharmacists.

A novel one-pot protocol for the convenient and efficient synthesis of (2-phenylimidazo[1,2-a]pyridin-3-yl)alkane-1,2-diones (3) in good yields (32-88%) from 2-phenylimidazo[1,2-a]pyridines (1) and terminal alkynes (2) has been established with a wide range of substrate scope. A tandem reaction sequence containing gold-catalyzed double oxidations of terminal alkynes to generate glyoxals, nucleophilic addition of 2-phenylimidazo[1,2-a]pyridines to glyoxals to yield α-hydroxyl ketones, and oxygenation of the α-hydroxyl ketones to afford the final products 3 under air atmosphere is involved in this method. Simple operation, mild reaction conditions, and widely available substrates make this strategy more affordable.

Two new compounds classified as one new lumazine peptide, penilumamide K (1) and one new sesquiterpene (2), were obtained from the deep-sea derived fungus Aspergillus sp. SCSIO 41029, together with eleven known compounds (3−13). The structures of 1−13 including absolute configurations were determined by detailed NMR spectroscopy, HR-ESI-MS, chemical derivatization, and optical rotation data. Among them, compound 1 represents the first lumazine peptide reported from deep-sea derived fungus. The bioactive assay exhibited that compounds 1, 3, 4, 5, 7 and 10 had significant potency against α-glucosidase with IC50 values ranging from 18.61 to 109.06 μΜ. In addition, compounds 4 and 9 showed strong antibacterial activity against Staphylococcus aureus with MIC values of 0.78 and 6.25 μg ml−1, respectively.

Twelve indole alkaloids, including α-cyclopiazonic acid (CPA) (1), nine 2-oxo indole CPA derivatives (2–10), and two open-ring indole CPA derivatives (11 and 12), were isolated from the fermentatio...

Two new compounds, asperbenzophenone A (1) and versicolamide C (5), together with fifteen known compounds were isolated from a soft coral derived fungus Aspergillus sp. SCSIO 41036. Their structures were elucidated by spectroscopic methods, ECD analysis, and by a comparison with data from the literature. In bioassay, compound 8 showed significant inhibitory activity against lipopolysaccharide-inducted nitric oxide (NO) in RAW264.7 cells at the concentration of 10 μM. Additionally, the anti-acetylcholinesterase activity assay showed that 14 exhibited weak inhibition with an IC

A novel one-pot protocol for the convenient and efficient synthesis of (2-phenylimidazo[1,2

Asperpentenone A (1), a novel polyketide with a rare cyclopentenone-tetrahydrofuran moiety, was isolated along with eight known compounds (2–9) from the deep-sea derived fungus Aspergillus sp. SCSIO 41024. Their structures including absolute configurations were determined by extensive analysis of their spectroscopic analysis and X-ray crystallography. Biological evaluation results revealed that kojic acid (3) showed weak antibacterial activities against Bacillus thuringiensis and Acinetobacter baumannii with MIC values of 32 and 128 μg/mL, respectively. Furthermore, griseofamine A (9) exhibited weak antibacterial activity with an MIC value of 64 μg/mL against Escherichia coli. The results of antibacterial experiments and especially the large yield of kojic acid (3) indicated that kojic acid might represent a candidate precursor for the development of antimicrobial agents.

Iakyricidins A-D (1-4), a carbonyl-containing piericidin derivative and three novel piericidin analogues bearing cyclic skeletons, were isolated from the mangrove sediment derived strain Streptomyces iakyrus SCSIO NS104. These structures were established by spectroscopic techniques, Mosher's method, and ECD calculations. Compounds 2-4 represent a novel skeleton of piericidins with branched chain C-C cyclization, and their biosynthetic pathways are proposed. Compound 1, the first natural carbonyl-containing piericidin derivate, exhibited potent antiproliferative activity against ACHN with an IC50 value of 20 nM.

Anti-renal cell carcinoma (RCC) agents with new mechanisms of action are urgently needed. Twenty-seven natural products of the piericidin class, including 17 new ones, are obtained from a marine-derived Streptomyces strain, and several of them show strong inhibitory activities against ACHN renal carcinoma cells. By exploring the mechanisms of two representative natural piericidin compounds, piericidin A (PA) and glucopiericidin A (GPA), peroxiredoxin 1 (PRDX1) is detected as a potential target by transcriptome data of PA-treated ACHN cells, as well as the paired RCC tumor versus adjacent nontumor tissues. PA and GPA induce cell apoptosis through reducing the reactive oxygen species level caused by upregulated PRDX1 mRNA and protein level subsequently and exhibit potent antitumor efficacy in nude mice bearing ACHN xenografts, with increasing PRDX1 expression in tumor. The interaction between PA/GPA and PRDX1 was supported by the docking analysis and surface plasmon resonance. Moreover, the translocation of PRDX1 into the nucleus forced by PA/GPA is proposed to be a key factor for the anti-RCC procedure. Piericidins provide a novel scaffold for further development of potent anti-RCC agents, and the new action mechanism of these agents targeting PRDX1 may improve upon the limitations of existing targeted drugs for the treatment of renal cancer.

Five new compounds, including one bisabolane-type sesquiterpenoids, namely aspergillusene D (1), two new xanthones (2 and 3), and two new catecholderivatives (4 and 5), together with fourteen known compounds (6–19), were isolated and identified from the fungus Aspergillus sydowiiSCSIO 41,301 from the sponge Phakellia fusca. Their structures and absolute configurations were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. Most of the isolated compounds (1–3, and 6–19) were evaluated for their antiviral, cytotoxic, and antibacterial activities. Among them, new compounds 2 and 3 displayed obvious selective inhibitory activities against two influenza A virus subtypes, including A/Puerto Rico/8/34 (H1N1) and A/FM-1/1/47 (H1N1), with IC50 values ranging from 2.17 ± 1.39 to 4.70 ± 1.11 μM.

A transition-metal-free insertion of benzyl group between aldehyde and imidazole of 2-(1H-benzo[d]imidazol-1-yl)benzaldehyde was achieved for the first time. Two diverse sets of quinolin-4-one derivatives: benzo[4,5]imidazo[1,2-a]quinolin-5(7H)-ones (2) and 3-arylquinolin-4-ones (3) were synthesized based on identical starting materials 2-(1H-benzo[d]imidazol-1-yl)benzaldehydes (1) and benzyl bromides. In the preparations, two key intermediates I and II were involved and might be synthesized in situ through the reaction of an intra-Breslow intermediate with benzyl bromide via an enol attack in the presence of base or a NHC-based enamine attack in the absence of base, respectively, in which the intra-Breslow intermediate might function as a nucleophilic reagent by following two novel different pathways.

Under the guidance of MS/MS based molecular networking, bisorbicillchaetones A-C, three undescribed hybrid sorbicillinoids, were isolated from cultures of the deep-sea derived fungus Penicillium sp. SCSIO06868. The planar structures and absolute configurations of these compounds were determined by extensive spectroscopic analyses. Bisorbicillchaetones are the first examples of hybrid sorbicillinoids containing a coniochaetone unit. Bisorbicillchaetones A and B exhibited moderate inhibitory effect on NO production in LPS activated RAW264.7 cells with the IC

In devotion to investigating structurally novel and biologically active marine natural products, a dimer of a zinc complex, dizinchydroxyneoaspergillin (1), aspernones A–E (2–6), five cyclopentenone derivatives together with known polyketides (7–10), and neoaspergillic acid analogues (11–14) were isolated from the sponge-associated fungus Aspergillus ochraceopetaliformis SCSIO 41018. Their structures were elucidated on the basis of spectroscopic analysis, electronic circular dichroism (ECD) analysis, and X-ray diffraction. Dizinchydroxyneoaspergillin (1) displayed significant bactericide effects toward methicillin-resistant Staphyloccocus aureus, Staphyloccocus aureus, Enterococcus faecalis, Acinetobacter baumannii, and Klebsiella pneumonia with MIC values of 0.45–7.8 μg/mL and moderate in vitro cytotoxic activities against the K562, BEL-7402, and SGC-7901 cell lines with IC50 values of 12.88 ± 0.14, 15.83 ± 0.23, and 15.08 ± 0.62 μM, respectively. This is the first time to report the dimer of the zinc complex of hydroxyneoaspergillic acid conjunction at Zn–N-4 by a coordination bond. Additionally, compound 1 displayed significant antibacterial and cytotoxic activities, which would be a promising drug lead and could attract much attention from both chemists and pharmacists.

A pair of novel lipopeptide epimers, sinulariapeptides A (1) and B (2), and a new phthalide glycerol ether (3) were isolated from the marine algal-associated fungus Cochliobolus lunatus SCSIO41401, together with three known chromanone derivates (4&ndash, 6). The structures of the new compounds, including the absolute configurations, were determined by comprehensive spectroscopic methods, experimental and calculated electronic circular dichroism (ECD), and Mo2 (OAc)4-induced ECD methods. The new compounds 1&ndash, 3 showed moderate inhibitory activity against acetylcholinesterase (AChE), with IC50 values of 1.3&ndash, 2.5 &mu, M, and an in silico molecular docking study was also performed.

Four undescribed polyketide derivatives, named arthproliferins A-D (1-4), and one undescribed phenylspirodrimane derivative, named arthproliferin E (7), along with 11 known metabolites (5, 6, 8-16) were isolated from the soft coral-associated fungus Stachybotrys chartarum SCSIO41201. Their structures were determined through spectroscopic methods, X-ray crystallography, and ECD analysis. Compounds 1 and 3-15 were evaluated for their cytotoxic, and antibacterial activities. Among them, compounds 1 and 15 displayed moderate inhibitory activity against methicillin-resistant Staphylococcus aureus ATCC 29213 with an MIC value of 78 and 39 µg/mL, respectively. Furthermore, compound 15 displayed strong cytotoxic activities against the tested cell line with IC50 values less than 39 nM.

Two new compounds classified as one new lumazine peptide, penilumamide K (1) and one new sesquiterpene (2), were obtained from the deep-sea derived fungus Aspergillus sp. SCSIO 41029, together with eleven known compounds (3-13). The structures of 1-13 including absolute configurations were determined by detailed NMR spectroscopy, HR-ESI-MS, chemical derivatization, and optical rotation data. Among them, compound 1 represents the first lumazine peptide reported from deep-sea derived fungus. The bioactive assay exhibited that compounds 1, 3, 4, 5, 7 and 10 had significant potency against α-glucosidase with IC

Two new compounds, 5-[2-hydroxypropane-1-yl]-2,6-dimethlbenzene-1,3-diol (1) and coniochaetone L (2), together with 19 known compounds (3–21), were isolated from a deep-sea fungus, Penicillium sp. ...

Gilluones A–C (1–3), three new phloroglucinol heterodimers, asterriquinones I–K (4–6), three new bis-indolylquinones, and asterriquinols G–I (7–9), three new bis-indolylbenzenoids, were isolated from the sponge-derived fungus Aspergillus sp. SCSIO 41018 together with five known bis-indolyl alkaloids (10–14). Their structures were determined by detailed spectroscopic analyses, X-ray diffraction, a modified Mosher's method and electronic circular dichroism analysis. Gilluone A (1) possessed an unprecedented heterodimer polyketide skeleton fused by intermolecular [4 + 2] Diels–Alder cycloaddition featuring a novel cage structure bearing ketal and hemiketal functionalities. Gilluone B (2) possessed a heterodimer acyl phloroglucinol featuring amino and ester groups. Compared with previous bis-indolylquinones, asterriquinone I (5) represented the first reported bis-indolylquinone possessing a chlorine atom. Asterriquinones I–K (4–6) displayed cytotoxic activities against K562, BEL-7042, SGC-7901, A549, and HeLa cell lines. A possible biosynthetic pathway for gilluones A–C (1–3) was proposed.

Using the previously designed biphenyl-2-ylphosphine ligand, featuring a remote tertiary amino group, the first gold-catalyzed intermolecular hydroalkenylation of alkynes has been developed. Synthetically valuable conjugated dienyl alcohols are formed in moderate to good yields. A range of alkenyltrifluoroborates are allowed as the alkenyl donor, and no erosion of alkene geometry and/or the propargylic configuration are detected. DFT calculations confirm the critical role of the remote basic group in the ligand as a general-base catalyst for promoting this novel gold catalysis with good efficiency.

Seven new compounds, including four new chlorinated diphenyl ethers, namely chrysines A–D ( 1 – 4 ), one new dichlorinated xanthone, chrysoxanthone ( 5 ), dichloroorcinol ( 6 ), and one new benzeneacetic acid derivative, 3-isopentyl-4-hydroxy phenylacetic acid methyl ester ( 7 ), along with fourteen known compounds ( 8 – 21 ), were isolated from a deep-sea-derived fungus Penicillium chrysogenum SCSIO 41001. Their structures were determined by extensive spectroscopic methods and X-ray single-crystal diffraction analysis. All of the isolated compounds ( 1 − 21 ) were evaluated for their α-glucosidase inhibitory activity using PNPG method. Among them, nine compounds ( 2 , 3 , 5 , 6 , 8 , 9 , 13 , 17 , and 18 ) exhibited inhibitory activity against α-glucosidase with IC 50 values of 0.35, 0.20, 0.04, 0.16, 0.15, 0.09, 0.14, 0.14, and 0.12 mM, respectively (IC 50 0.28 mM for the positive control acarbose).

Four new prenylated indole alkaloids (1–4), and four new chromone derivatives (7–10), together with six known compounds (5, 6, and 11–14), have been isolated from the mangrove sediment derived fungus Penicillium sp. SCSIO041218, cultured in the 1% NaCl PDB substrate. The structures of new compounds were determined by analysis of the NMR and MS spectroscopic data. The absolute configuration of the prenylated indole alkaloids were elucidated based on the comparison of ECDs with known analogues. The absolute configurations of the chromone derivatives were determined by time-dependent density functional theory calculations of the ECD spectra. In all of these isolated compounds, penixanthones A and B (12 and 13) exhibited antiallergic activities in vitro.

Penicildiones A-D (1-4), four new steroids derivatives together with three known compounds including 16α-methylpregna-17α,19-dihydroxy-(9,11)-epoxy-4-ene-3,18-dione-20-acetoxy (5), stachybotrylactone B (6) and stachybotrin (7) were isolated from the soft coral-derived fungus Penicillium sp. SCSIO41201, cultured in the 1% NaCl PDB substrate. Their structures were determined through spectroscopic methods and X-ray crystallography. Biological evaluation results revealed that 6 exhibited significant cytotoxic activity against HL-60, K562, MOLT-4, ACHN, 786-O, and OS-RC-2 cell lines with IC50 values of 5.23, 4.12, 4.31, 23.55, 7.65 and 10.81 μmol·L-1, respectively, while other compounds showed weak or no cytotoxicity at 50 μmol·L-1.

Two novel sorbicillinoid adducts containing bicyclo[2.2.2]octane and tetrahydrofuran moieties, named sorbicillfurans A and B (1 and 2), were isolated from the static culture of the marine-derived fungus Penicillium citrinum SCSIO41402. Their structures including absolute configurations were determined by spectroscopic and calculated ECD analyses. Sorbicillfurans A and B (1 and 2) are the first examples of sorbicillinoids possessing a tetrahydrofuran unit. In the proposed biosynthetic pathway, sorbicillfuran B (2), harboring a rare and complex polycyclic framework, is probably formed by two Diels-Alder reactions. Both isolates were evaluated for the cytotoxicity against six human cancer cell lines, only sorbicillfuran B (2) showed weak cytotoxicity against HL-60 cells with an IC50 value of 9.6 μM.

Iakyricidins A-D (

Six undescribed 4-quinolone alkaloids, including four racemic mixtures, (±)-oxypenicinolines A−D, and two related ones, penicinolines F and G, together with seven known analogues, were isolated from the mangrove-derived fungus Penicillium steckii SCSIO 41025 (Trichocomaceae). The racemates were separated by HPLC using chiral columns. Their structures including absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) experiments, and single-crystal X-ray diffraction analysis. Structurally, (±)-oxypenicinolines A−D shared with an unusual 6/6/5/5 tetracyclic system incorporating a rare tetrahydro-pyrrolyl moiety. A plausible biosynthetic pathway for pyrrolyl 4-quinolone alkaloids is proposed. (±)-oxypenicinoline A and quinolactacide displayed α-glucosidase inhibitory activity with the IC50 values of 317.8 and 365.9 μΜ, respectively, which were more potent than that of acarbose (461.0 μM). Additionally, penicinoline and penicinoline E showed weak inhibitions toward acetylcholinesterase (AChE).

An unexpected ring-contraction from benzo[b]pyrazino[1,2-d][1,4]thiazine-1,4-diones (6) to benzo[4,5]thiazolo[3,2-a]pyrazine-1,4-diones (7) has been developed. The preliminary mechanistic studies showed the transformation contained two independent steps: the first step is the formation of a Michael adduct upon the addition of the protic solvent, in the presence of base, to the C-2-C-3 double bond of compound 6, and the second step is a ring-contraction induced by oxygen via the migration of sulfur atom from C-2 to C-3 position. And its scope is also studied.

Three dimeric nitrophenyl trans-epoxyamides, chrysamides A-C (1-3), were obtained from the deep-sea-derived fungus Penicillium chrysogenum SCSIO41001. Their structures were characterized by spectroscopic analysis, electronic circular dichroism computations, and X-ray single-crystal diffraction analysis. Notably, compound 1 possesses a novel centrosymmetric dimer skeleton featuring an unprecedented 7-oxa-2,5-diazabicyclo[2.2.1]heptane ring system, which represents the first example of dimeric nitrophenyl trans-epoxyamide in nature. Compound 3 suppresses the production of proinflammatory cytokine interleukin-17. A possible biosynthetic pathway of 1-3 was proposed.

Phytopathogenic fungi remain a continuous and huge threat in the agricultural fields. The agrochemical industry has made great development of the use of microbial natural products, which has been regarded as an effective strategy against phytopathogenic fungi. Antifungal bioassay-directed fractionation was used to isolate two new oxepine-containing alkaloids (1 and 2), two new 4-aryl-quinolin-2-one alkaloids (3 and 4), and four new prenylated xanthones (5-8) from the deep-sea-derived fungus Aspergillus versicolor SCSIO 05879. Extensive NMR spectroscopic analysis, quantum mechanical calculations, and X-ray single-crystal diffraction were used to elucidate their structures, including their absolute configurations. Versicoloids A and B, versicone A, and cottoquinazoline A showed antifungal activities against three phytopathogenic fungi. The antifungal activities of these bioactive compounds strongly depend on the fungal species. Especially versicoloids A and B showed strong fungicidal effect (MIC of 1.6 μg/mL) against Colletotrichum acutatum, compared with that of the positive control cycloheximide (MIC of 6.4 μg/mL). The results of antifungal experiments indicated that versicoloids A and B may be regarded as candidate agents of antifungal agrochemicals.

Terminal allylic alcohols are important motifs in natural products, and also key intermediates/precursors in numerous novel reaction transformations. In this study, enabled by a bifunctional ligand featuring a basic amino group, a gold-catalyzed hydroarylation of terminal unactivated propargylic alcohols with heteroareneboronic acids has been first established, and efficiently affords various terminal aryl-substituted allylic alcohols with moderate to high yields under mild conditions.

Two new alkaloids, fumigatosides E (1) and F (2), and a new natural product, 3, 7-diketo-cephalosporin P1 (6) along with five known compounds (3&ndash, 5, 7, 8) were isolated from deep-sea derived fungal Aspergillus fumigatus SCSIO 41012. Their structures were determined by extensive spectroscopic data analysis, including 1D, 2D nuclear magnetic resonance (NMR) and mass spectrometry (MS), and comparison between the calculated and experimental electronic circular dichroism (ECD) spectra. In addition, all compounds were tested for antibacterial and antifungal inhibitory activities. Compound 1 showed significant antifungal activity against Fusarium oxysporum f. sp. momordicae with MIC at 1.56 &micro, g/mL. Compound 4 exhibited significant higher activity against S. aureus (16,339 and 29,213) with MIC values of 1.56 and 0.78 &micro, g/mL, respectively, and compound 2 exhibited significant activity against A. baumanii ATCC 19606 with a MIC value of 6.25 &micro, g/mL.

Aranciamycin K (1) and isotirandamycin B (2) were isolated from a marine-derived Streptomyces sp. SCSIO 41399, along with the previously reported four anthracycline derivatives (3-6), and two known tirandamycin derivatives (7 and 8). Their structures including absolute configurations were determined by extensive analysis of their spectroscopic analysis and ECD calculation method. Most of the isolated compounds were tested for their cytotoxic, antibacterial, and antifungal activities. Compounds 2, 7 and 8 displayed potent bacteriostatic effects against Streptococcus agalactiae with MIC values of 11.5, 5.9 and 5.7 μM, respectively. Besides, compounds 3, 5 and 6 exhibited moderate in vitro cytotoxic activities against the K562 cell lines with IC50 values of 22.0 ± 0.20, 1.80 ± 0.01 and 12.1 ± 0.07 μM, respectively.

A one-pot multicomponent approach was established for site selective synthesis of novel 1,3,6-trisubstituted 3,6-diunsaturated (3Z,6Z)-2,5-diketopiperazine derivatives with high stereoselectivity. The computational studies revealed that the steric hindrances between the 2-hydrogen atoms on the aromatic rings and the carbonyl, as well as the steric repulsions between the hydrogen atoms of the CH group in the benzylidene and the CH2 group in the N-alkylative part might be responsible for the Z/E selectivity. Compound (3Z,6Z)-3h (IC50=11 nM) has a close activity to the positive compound plinabulin (IC50=15 nM) against the cancer cell line HL60.