Synthesis and biological activity of new bisbenzofuran-imidazolium salts

A series of novel bisbenzofuran-imidazolium salts were designed and prepared. The in vitro antitumor activity of these derivatives was evaluated against a panel of human tumor cell lines (A549, HL-60, MCF-7, SMMC-7721 and SW480). Results demonstrated that 2-methyl-benzimidazole ring and substitution of the imidazolyl-3-position with a 4-methoxyphenacyl or 2-naphthylacyl substituent were important for promoting cytotoxic activity. Notably, compound 23 was found to be the most potent compound with IC₅₀ values of 0.64–1.47 μM against five human tumor cell lines, and exhibited higher selectivity to MCF-7 and SW-480 cell lines with IC₅₀ values 15.3-fold and 9.1-fold lower than DDP.     

Synthesis,biological evaluation and molecular docking studies of aminochalcone derivatives as potential anticancer agents by targeting tubulin colchicine binding site

A series of aminochalcone derivatives have been synthesized, characterized by HRMS, ¹H NMR and ¹³C NMR and evaluated for their antiproliferative activity against HepG2 and HCT116 human cancer cell lines. The most of new synthesized compounds displayed moderate to potent antiproliferative activity against test cancer cell lines. Among the derivatives, compound 4 displayed potent inhibitory activity with IC₅₀ values ranged from 0.018 to 5.33 μM against all tested cancer cell lines including drug resistant HCT-8/T. Furthermore, this compound showed low cytotoxicity on normal human cell lines (LO2). The in vitro tubulin polymerization assay showed that compound 4 inhibited tubulin assembly in a concentration-dependent manner with IC₅₀ value of 7.1 μM, when compared to standard colchicine (IC₅₀ = 9.0 μM). Further biological evaluations revealed that compound 4 was able to arrest the cell cycle in G2/M phase. Molecular docking study demonstrated the interaction of compound 4 at the colchicine binding site of tubulin. All the results indicated that compound 4 is a promising inhibitor of tubulin polymerization for the treatment of cancer.     

Novel benzotriazole N-acylarylhydrazone hybrids: Design,synthesis, anticancer activity,effects on cell cycle profile,caspase-3 mediated apoptosis and FAK inhibition

A series of novel benzotriazole N-acylarylhydrazone hybrids was synthesized according fragment-based design strategy. All the synthesized compounds were evaluated for their anticancer activity against 60 human tumor cell lines by NCI (USA). Five compounds: 3d, 3e, 3f, 3o and 3q exhibited significant to potent anticancer activity at low concentrations. Compound 3q showed the most prominent broad-spectrum anticancer activity against 34 tumor cell lines, with mean growth inhibition percent of 45.80%. It exerted the highest potency against colon HT-29 cell line, with cell growth inhibition 86.86%. All leukemia cell lines were highly sensitive to compound 3q. Additionally, compound 3q demonstrated lethal activity to MDA-MB-435 belonging melanoma. Compound 3e exhibited the highest anticancer activity against leukemic CCRF-CEM and HL-60(TB) cell lines, with cell growth inhibition 86.69% and 86.42%, respectively. Moreover, it exerted marked potency against ovarian OVCAR-3 cancer cell line, with cell growth inhibition 78.24%. Four compounds: 3d, 3e, 3f and 3q were further studied through determination of IC₅₀ values against the most sensitive cancer cell lines. The four compounds exhibited highly potent anticancer activity against ovarian cancer OVCAR-3 and leukemia HL-60 (TB) cell lines, with IC₅₀ values in nano-molar range between 25 and 130 nM. They showed 18–2.3 folds more potent anticancer activity than doxorubicin. The most prominent compound was 3e, (IC₅₀ values 29 and 25 nM against OVCAR-3 and HL-60 (TB) cell lines, respectively), representing 10 and 18 folds more potency than doxorubicin. The anti-proliferative activity of these four compounds appeared to correlate well with their ability to inhibit FAK at nano-molar range between 44.6 and 80.75 nM. Compound 3e was a potent, inhibitor of FAK and Pyk2 activity with IC₅₀ values of 44.6 and 70.19 nM, respectively. It was 1.6 fold less potent for Pyk2 than FAK. Additionally, it displayed inhibition in cell based assay measuring phosphorylated-FAK (IC₅₀ = 32.72 nM). Inhibition of FAK enzyme led to a significant increase in the level of active caspase-3, compared to control (11.35 folds), accumulation of cells in pre-G1 phase and annexin-V and propidium iodide staining in addition to cell cycle arrest at G2/M phase indicating that cell death proceeded through an apoptotic mechanism.     

Synthesis of substituted biphenyl methylene indolinones as apoptosis inducers and tubulin polymerization inhibitors

A new series of biphenyl methylene indolinones has been designed, synthesized and evaluated for their in vitro antiproliferative activity against various cancer cell lines like DU-145 (prostate cancer cell line), 4T1 (mouse breast cancer cell line), MDA-MB-231 (human breast cancer cell line), BT-549 (human breast cancer cell line), T24 (human urinary bladder carcinoma cell line), and HeLa (cervical cancer cell line). Among the series, compound 10e showed potent in vitro cytotoxic activity against HeLa and DU-145 cancer cell lines with IC₅₀ value of 1.74 ± 0.69 µM and 1.68 ± 1.06 µM respectively. To understand the underlying mechanism of most potent cytotoxic compound 10e, various mechanistic studies were carried out on DU-145 cell lines. Cell cycle analysis results revealed that these conjugates affect both G0/G1 and G2/M phase of the cycle, tubulin binding assay resulted that compound 10e interrupting microtubule network formation by inhibiting tubulin polymerization with IC₅₀ value of 4.96 ± 0.05 μM. Moreover, molecular docking of 10e on colchicine binding site of the tubulin explains the interaction of 10e with tubulin. Clonogenic assay indicated inhibition of colony formation by compound 10e in a dose dependent manner. In addition, morphological changes were clearly observed by AO/EB and DAPI staining studies. Moreover, ROS detection using DCFDA, JC-1, and annexin V-FITC assays demonstrated the significant apoptosis induction by 10e.     

Synthesis and cytotoxic activities of novel hybrid 2-phenyl-3-alkylbenzofuran and imidazole/triazole compounds

A series of novel hybrid compounds of 2-phenyl-3-alkylbenzofuran and imidazole or triazole were prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the 2-ethyl-imidazole ring, and substitution of the imidazolyl-3-position with a 2-bromobenzyl or naphthylacyl group, were vital for modulating inhibitory activity. In particular, hybrid compound 31 was found to be the most potent derivative with IC₅₀ values of 0.08–0.55 μM against five strains human tumor cell lines and was found to be more selective against breast carcinoma (MCF-7) and colon carcinoma (SW480) (IC₅₀ values 40.8-fold and 40.1-fold lower than cisplatin (DDP)).     

Artemisinin-indole and artemisinin-imidazole hybrids: Synthesis,cytotoxic evaluation and reversal effects on multidrug resistance in MCF-7/ADR cells

A series of artemisinin derivatives with MDR reversal activity were designed and synthesized. All hybrids were screened to anticancer activities against four human cancer cell lines (A549, MCF-7, HepG-2, MDA-MB-231) and normal human hepatic cell (L02) in vitro. Most of the new compounds showed higher anticancer activities than artemisinin, among which compounds 11a and 11c displayed superior potency with IC₅₀ 6.78?μM and 5.25?μM against MCF-7, respectively. The further research indicated that the most potent 11c induced cell cycle arrest at G2 phase in MCF-7. Additionally, compound 11c showed remarkable MDR reversal activity which reversed adriamycin against MCF-7/ADR cells with IC₅₀ 0.76?μM.     

Synthesis of (Z)-3-(arylamino)-1-(3-phenylimidazo[1,5-a]pyridin-1-yl)prop-2-en-1-ones as potential cytotoxic agents

The new derivatives based on (Z)-3-(arylamino)-1-(3-phenylimidazo[1,5-a]pyridin-1-yl)prop-2-en-1-one scaffold was synthesized and evaluated for their in vitro cytotoxic potential against a panel of cancer cell lines, viz., A549 (human lung cancer), HCT-116 (human colorectal cancer), B16F10 (murine melanoma cancer), BT-474 (human breast cancer), and MDA-MB-231 (human triple-negative breast cancer). Among them, many of the synthesized compounds exhibited promising cytotoxic potential against the panel of tested cancer cell lines with IC₅₀ <30 µM. Based on the preliminary screening results, the structure-activity relationship (SAR) of the compounds was established. Among the synthesized compounds, 15i displayed a potential anti-proliferative activity against HCT-116 cancer cell line with an IC₅₀ value of 1.21 ± 0.14 µM. Flow cytometric analysis revealed that compound 15i arrested the G0/G1 phase of the cell cycle. Moreover, increased reactive oxygen species (ROS) generation, clonogenic assay, acridine orange staining, DAPI nuclear staining, measurement of mitochondrial membrane potential (ΔΨm), and annexin V-FITC assays revealed that compound 15i promoted cell death through apoptosis.     

New biphenyl derivatives from the leaves of Nicotiana tabacum and their cytotoxic activity

With the aim of searching for new bioactive metabolites from medicinal plants, three new biphenyls, tababiphenyls G–I (1–3), together with four known ones (4–7) were isolated from the leaves of Nicotiana tabacum. Their structures were elucidated by extensive NMR and MS spectroscopic analyses. All the isolated compounds were evaluated for their cytotoxicity against NB4, A549, SHSY5Y, PC3, and MCF7 human cancer cell lines, and some of them showed moderate inhibitory activities against several human tumor cell lines with IC₅₀ values ranging from 2.8 to 9.4 μM.     

Design and molecular modeling of novel P38α MAPK inhibitors targeting breast cancer,synthesized from oxygen heterocyclic natural compounds

Two new series of furochromone and benzofuran derivatives were designed, synthesized and evaluated for their in vitro anticancer activity against MCF-7 and MDA231 breast cancer cell lines. Compounds 5, 6, 7, 9, 15a, 16, 17a and 18 exhibited the best antiproliferative activities with IC₅₀ values ranging from 1.19 to 2.78?µM against MCF-7 superior to lapatinib as reference standard (IC₅₀; 4.69?µM). Compounds 15a and 18 revealed significant cytotoxic activity against MCF-7 and MDA231, therefore their inhibitory potencies against p38α MAP kinase were evaluated. Remarkably they exhibited significant IC₅₀ of 0.04?µM comparable to SB203580 (IC₅₀; 0.50?µM) as a reference standard. These promising results of cytotoxic activity and significant inhibition of p38α MAP kinase, were confirmed by exploring the effect of benzofuran derivative (18) on the apoptotic induction and cell cycle progression of MCF-7 cell line. Compound 18 induced preG1 apoptosis and cell growth arrest at G2/M phase preventing the mitotic cycle. Moreover it activated the caspase-7 which executes apoptosis. Molecular docking study was carried out using GOLD program to predict the mode of binding interaction of the synthesized compounds into the target p38α MAPK. Additionally, the physicochemical properties and ADME parameters of compound 18 were examined in silico to investigate its drug-likeness.     

C21 steroidal glycosides with cytotoxic activities from Cynanchum otophyllum

Eight new C21 steroidal glycosides, namely cynanotins A–H (1–8), together with fifteen known analogues, were isolated from the roots of Cynanchum otophyllum. Their structures were elucidated by spectroscopic analysis and chemical methods. In this study, all of isolates were tested for their vitro inhibitory activities against five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480). Compounds 3–15 showed moderate cytotoxic activities against HL-60 cell lines with IC₅₀ values ranging from 11.4 to 37.9?µM. Compounds 5, 9, and 10 showed marked or moderate cytotoxic activities against five human tumor cell lines with IC₅₀ values ranging from 11.4 to 36.7?µM. Compound 11 displayed moderate cytotoxic activities against HL-60, SMMC-7721, MCF-7 and SW480 cell lines with IC₅₀ values of 12.2–30.8?µM. Compared to the positive control (IC₅₀: 35.0?µM), compounds 5, 9–11 exhibited more potential inhibitory activity against MCF-7 cells (IC₅₀: 16.1–25.6?µM).     

Synthesis,biological evaluation and molecular docking studies of trans-indole-3-acrylamide derivatives,a new class of tubulin polymerization inhibitors

In this study, we synthesized a series of trans-indole-3-acrylamide derivatives (3a–k) and investigated their activity for inhibition of cell proliferation against five human cancer cell lines (HeLa, MCF7, MDA-MB-231, Raji and HL-60) by MTT assay. Compound 3e showed significant antiproliferative activity against both the Raji and HL-60 cell lines with IC₅₀ values of 9.5 and 5.1 μM, respectively. Compound 3e also exhibited moderate inhibitory activity on tubulin polymerization (IC₅₀ = 17 μM). Flow cytometric analysis of cultured cells treated with 3e also demonstrated that the compound caused cell cycle arrest at the G2/M phase in HL-60 and HeLa cells. Moreover, 3e, the most active compound, caused an apoptotic cell death through the activation of caspase-3. Docking simulations suggested that 3e binds to the colchicine site of tubulin.     

Meeting organometallic chemistry with drug discovery: CH activation enabled discovery of a new ring system of 12H-Indazolo[2,1-a]cinnolin-12-ones with anti-proliferation activity

A diverse library of new ring system 12H-indazolo[2,1-a]cinnolin-12-ones have been synthesized efficiently via Ru (II) and Rh (III) catalyzed tandem CH alkylation/[4 + 2] annulation with diazo compounds in high to excellent yields. For the first time, we evaluated the biological activity of these compounds with this new skeleton and found some compounds exhibited high cytotoxic activity against human PC-3 and PANC-1 tumor cell lines with nanomolar IC₅₀. Among them, the most potent compound 36 showed broad-spectrum cytotoxic activities against a series of human tumor cell lines derived from different organs (IC₅₀ ~ 41 to 197 nM). Moreover, preliminary mechanistic studies indicated that 36 could inhibit the colony formation, cause cell cycle arrest and induce apoptosis of PC-3 cancer cells in a dose-dependent manner. Further intracellular mechanisms investigation found that 36 treatments could dose-dependently decrease the levels of caspase-3 and PARP and up-regulate the level of cleaved PARP. These results suggested that 36 is a novel compound with good potential in the treatment of human cancers and worthy of further investigation.     

Synthesis,biological evaluation and molecular docking of benzimidazole grafted benzsulfamide-containing pyrazole ring derivatives as novel tubulin polymerization inhibitors

Tubulin-targeting drugs have increasingly become the focus of anticancer drugs research. Twenty-five novel benzimidazole grafted benzsulfamide-containing pyrazole ring derivatives were synthesized and evaluated for bioactivity as potential tubulin polymerization inhibitors. Among them, compound 30 showed the most excellent inhibition against tubulin assembly (IC₅₀?=?1.52?μM) and in vitro growth inhibitory activity against a panel of four human cancer cell lines (IC₅₀?=?0.15, 0.21, 0.33 and 0.17?μM, respectively for A549, Hela, HepG2 and MCF-7). It could also validly induce A549 cell apoptosis, cause cell cycle arrest in G2/M phase and disrupt the cellular microtubule network. These results, along with molecular docking data, provided an important basis for further optimization of compound 30 as a potential anticancer agent.     

Design and synthesis of various quinizarin derivatives as potential anticancer agents in acute T lymphoblastic leukemia

A series of quinizarin derivatives containing quaternary ammonium salts and/or thiourea groups were synthesized and their anticancer activities against leukemia cell lines have been tested. Results showed that most of quinizarin derivatives could inhibit the proliferation of leukemia cells. Among these derivatives, compound 3 showed good inhibition activity against various leukemia cells with IC₅₀ values ranging from 0.90?±?2.55?μM to 10.90?±?3.66?μM. At the same time, compound 3 also inhibited the growth of human embryonic kidney-293 cell (HEK-293). Molt-4 and Jurkat cells, acute T lymphoblastic leukemia (T-ALL) cell lines, were selected to reveal potential anticancer mechanism of compound 3. Compound 3 inhibited the proliferation of Molt-4 and Jurkat cells in a dose- and time-dependent manner and led to a marked G0/G1 phase arrest. Analysis of Annexin V-APC and intracellular reactive oxygen species (ROS) level by flow cytometry showed that compound 3 induced significant apoptosis in Molt-4 and Jurkat cells. Western blotting assay showed that compound 3 activated the caspase-dependent apoptosis pathway and induced the degradation of Bcl-2 and c-myc protein.     

Synthesis and biological evaluation of some novel thiobenzimidazole derivatives as anti-renal cancer agents through inhibition of c-MET kinase

Benzimidazole is an interesting scaffold constituting a main core in many anticancer agents against variable cell lines as Carbendazim (I) and Nocodazole (II). Accordingly, eighteen compounds of 2-((1H-benzoimidazol-2-yl)thio)-1-(aryl/heteroaryl)ethan-1-ones, in their sulfate salt and free forms, were designed and investigated as anticancer agents. In vitro preliminary screening of selected compounds by the National Cancer Institute (NCI) on a panel of 60 cell lines revealed renal cancer cell line (A498) as the most vulnerable cell line; accordingly, IC₅₀ values against A498 cell line were determined for compounds with the best results. The best inhibitory activity was for compound 4a with (IC₅₀ = 6.97 µM) compared to sunitinib as a reference drug (IC₅₀ = 6.99 µM). Compound 4a was further subjected to cell cycle analysis that indicated the decrease in cell population in the G2/M phase when compared to the untreated control cells. In addition, it showed significant increase in the late apoptosis in Annexin-V FTIC study compared to the control cells. An enzymatic inhibitory study on compound 4a against c-Met and MAP kinases revealed its better activity against c-Met kinase with (IC₅₀ = 0.27 µM) compared to sunitinib (IC₅₀ = 0.18 µM). Molecular docking study was conducted to reveal the interactions of compound 4a in the active site of c-Met kinase. Computational ADME study was performed to insure that compound 4a has proper pharmacokinetic and drug-likeness properties.     

VEGFR-2 inhibiting effect and molecular modeling of newly synthesized coumarin derivatives as anti-breast cancer agents

Twenty five newly synthesized coumarin scaffold based derivatives were assayed for their in vitro anticancer activity against MCF-7 breast and PC-3 prostate cancer cell lines and were further assessed for their in vitro VEGFR-2 kinase inhibitory activity. The in vitro cytotoxic studies revealed that most of the synthesized compounds possessed very promising cytotoxicity against MCF-7, particularly; compounds 4a (IC₅₀ = 1.24 µM) and 3d (IC₅₀ = 1.65 µM) exhibited exceptional activities superior to the positive control staurosporine (IC₅₀ = 8.81 µM). Similarly, the majority of the compounds exhibited higher antiproliferative activities compared to the reference standard with IC₅₀ values ranging from 2.07 to 8.68 µM. The two cytotoxic derivatives 4a and 3d were selected to evaluate their inhibitory potencies against VEGFR-2 kinase. Remarkably, compound 4a, exhibited significant IC₅₀ of 0.36 µM comparable to staurosporine (IC₅₀; 0.33 µM). Moreover, it was capable of inducing preG1 apoptosis, cell growth arrest at G2/M phase and activating caspase-9. On the other hand, insignificant cytotoxic activity was observed for all compounds towards PC-3 cell line. Molecular docking study was carried out for the most active anti-VEGFR-2 derivative 4a, which demonstrated the ability of the tested compound to interact with the key amino acids in the target VEGFR-2 kinase binding site. Additionally, the ADME parameters and physicochemical properties of compound 4a were examined in silico.     

Synthesis and biological evaluation of 2,4-disubstituted phthalazinones as Aurora kinase inhibitors

A series of 2,4-disubstituted phthalazinones were synthesized and their biological activities, including antiproliferation, inhibition against Aurora kinases and cell cycle effects were evaluated. Among them, N-cyclohexyl-4-((4-(1-methyl-1H-pyrazol-4-yl)-1-oxophthalazin-2(1H)-yl) methyl) benzamide (12c) exhibited the most potent antiproliferation against five carcinoma cell lines (HeLa, A549, HepG2, LoVo and HCT116 cells) with IC₅₀ values in range of 2.2–4.6?μM, while the IC₅₀ value of reference compound VX-680 was 8.5–15.3?μM. Moreover, Aurora kinase assays exhibited that compound 12c was potent inhibitor of AurA and AurB kinase with the IC₅₀ values were 118?±?8.1 and 80?±?4.2?nM, respectively. Molecular docking studies indicated that compound 12c forms better interaction with both AurA and AurB. Furthermore, compound 12c induced G2/M cell cycle arrest in HeLa cells by regulating protein levels of cyclinB1 and cdc2. These results suggested that 12c is a promising pan-Aurora kinase inhibitor for the potential treatment of cancer.     

Synthesis of stable benzimidazole derivatives bearing pyrazole as anticancer and EGFR receptor inhibitors

A new series of benzimidazole linked pyrazole derivatives were synthesized by cyclocondensation reaction through one-pot multicomponent reaction in absolute ethanol. All the synthesized compounds were tested for their in vitro anticancer activities on five human cancer cell lines including MCF-7, HaCaT, MDA-MB231, A549 and HepG2. EGFR receptor inhibitory activities were carried out for all the compounds. Majority of the compounds showed potent antiproliferative activity against the tested cancer cell lines. Compound 5a showed the most effective activity against the lungs cancer cell lines (IC₅₀ = 2.2 µM) and EGFR binding (IC₅₀ = 0.97 µM) affinity as compared to other members of the series. Compound 5a inhibited growth of A549 cancer cells by inducing a strong G₂/M phase arrest. In addition, same compound inhibited growth of A549 cancer cells by inducing apoptosis. In molecular docking studies compound 5a was bound to the active pocket of the EGFR (PDB 1M17) with five key hydrogen bonds and two π-π interaction with binding energies ΔG = −34.581 Kcal/mol.     

Quinazoline Based HSP90 Inhibitors: Synthesis,Modeling Study and ADME Calculations Towards Breast Cancer Targeting

A new 2-thioquinazolinones series was designed and synthesized as HSP90 inhibitors based on the structure of hit compound VII obtained by virtual screening approach. Their in vitro anti-proliferative activity was evaluated against three human cancer cell lines rich in HSP90 namely; colorectal carcinoma (HCT-116), and cervical carcinoma (Hela), breast carcinoma (MCF-7). Compounds 5a, 5d, 5e and 9h showed a significant broad spectrum anti-proliferative activity against all tested cell lines. They were characterized by potent effect against breast cancer in particular with IC₅₀ of 11.73, 8.56, 7.35 and 9.48 μM, respectively against Doxorubicin (IC₅₀ 4.17 μM). HSP90 ATPase activity inhibition assay were conducted where compound 5d exhibited the best IC₅₀ with 1.58 μM compared to Tanespimycin (IC₅₀ = 2.17 μM). Compounds 5a and 9h showed higher IC₅₀ values of 3.21 and 3.41 μM, respectively. The effects of 5a, 5d and 9h on Her2 (a client proteins of HSP90) and HSP70 were evaluated in MCF-7 cells. All tested compounds were found to reduce Her2 protein expression levels and induce Hsp70 protein expression levels significantly, emphasizing that antibreast cancer effect is a consequence of HSP90 chaperone inhibition. Cell cycle analysis of MCF-7 cells treated with 5d showed cell cycle arrest at G2/M phase 38.89% and pro-apoptotic activity as indicated by annexin V-FITC staining by 22.42%. Molecular docking studies suggested mode of interaction to HSP90 via hydrogen bonding. ADME properties prediction of the active compounds suggested that they could be used as orally absorbed anticancer drug candidates.     

Design,synthesis, and biological evaluation of pyrazole derivatives containing acetamide bond as potential BRAFV600E inhibitors

With the increasingly acquired resistance, relapse and side effects of known marketed BRAF^V600E inhibitors, it’s significant to design the more effective and novel drugs. In this study, a series of novel pyrazole derivatives containing acetamide bond had been designed and synthesized on the basis of analysis of the endogenous ligands extracted from the known B-Raf co-crystals in the PDB database. Then, the compounds were evaluated for biological activities as potential BRAF^V600E inhibitors. The bioassay results in vitro against three human tumor cell lines revealed that some of the compounds showed very impressed antiproliferative property. Among them, the compound 5r with IC₅₀ values of 0.10?±?0.01?μM against BRAF^V600E and 0.96?±?0.10?μM against A375 cell line, showed the most potent inhibitory effect, compared with the positive-controlled agents vemurafenib (IC₅₀?=?0.04?±?0.004?μM for BRAF^V600E, IC₅₀?=?1.05?±?0.10?μM against A375). Further investigation confirmed that the compound 5r could induce A375 cell apoptosis, induce A375 cell death through changing mitochondrial membrane potential, and result in A375 cell arrest at the G1 phase of the cell cycle. Docking simulations results indicated that the compound 5r could bind tightly at the BRAF^V600E active site. Meanwhile, 3D-QSAR model suggested that these compounds may be potential anticancer inhibitors. Overall, the article provided some new molecular scaffolds for the further BRAF^V600E inhibitors.