Novel Sulfanilamide as Potent Surfactants and Antibacterial Agents

Sulfanilamide derivatives of the type RØSO₂NHR in which substitution at both the amino and amido nitrogen have been synthesized where R = NHCOCH:CHCOOH, NHCOCH₂CH₂COOH, NHCH₂CH(OH)CH₂SO₃Na, N⁺(CH₃)₃I^? and NHCH₂CH(OH)CH₂N⁺(C₂H₅)₃Cl^? and R′ = butyl, cyclohexyl, and decyl. The unique structural features of these sulfanilamides were confirmed by infrared, proton magnetic resonance and elemental analysis. Most of these compounds exhibited good water solubility and surface activity. Wetting ability and tendency of enhancing oil/water emulsification were related to the structure of the substituents in sulfanilamide molecule. Furthermore, the peculiar of molecular structure of these sulfanilamide surfactants imparts distinguished antimicrobial activity to these molecular species against some Gram positive and Gram negative bacteria.     

Discovery of Novel Quinazoline Derivatives as Potent Antitumor Agents

In this work, we designed and synthesized a novel series of quinazoline derivatives 6–19 and then evaluated their broad-spectrum antitumor activity against MGC-803, MCF-7, PC-9, A549, and H1975, respectively. Most of them demonstrated low micromolar cytotoxicity towards five tested cell lines. In particular, compound 18 exhibited nanomolar level inhibitory activity against MGC-803 cells with an IC₅₀ value of 0.85 μM, indicating approximately a 32-fold selectivity against GES-1 (IC₅₀ = 26.75 μM). Further preclinical evaluation showed that compound 18 remarkably inhibited the migration of MGC-803 cells, induced cell cycle arrest at G2/M, and induced MGC-803 apoptosis, resulting in decreasing the expression of both Bcl-2 and Mcl-1, and up-regulating the expression of both Bax and cleaved PARP. No death or obvious pathological damage was observed in mice by acute toxicity assay. The in vivo antitumor evaluation suggested that compound 18 significantly decreased the average tumor volume and tumor weight without any effect on body weight, which is better than 5-Fu. Therefore, compound 18 can be used as a lead compound for the further development of antitumor drugs in the future.     

Novel Nitric Oxide Donor Dinitroazetidine-Coumarin Hybrids as Potent Anti-Intrahepatic Cholangiocarcinoma Agents

Intrahepatic cholangiocarcinoma (iCC) is a serious liver cancer threatening human health. However, there are a few chemotherapeutic drugs for the treatment of iCC in the clinic. It is extremely urgent to develop new drugs for iCC. In this study, twenty dinitroazetidine and coumarin hybrids were synthesized and evaluated anti-iCC bioactivity as a new type of nitric oxide (NO) donors. Among them, compounds 2–5 and 21 showed a higher antiproliferative activity against RBE cell lines (human intrahepatic cholangiocarcinoma cell lines) and low cytotoxicity in nontumor cells (HOSEpiC and T29). The preliminary study of pharmacology mechanism indicated that compounds 2–5 and 21 could release effective concentration of NO in RBE cell lines, which leaded to inhibit the proliferation of RBE cell lines. The research results revealed that compound 3 inhibited the proliferation of RBE cell lines by inducing apoptosis and arresting cell cycle at G₂/M phase. Additionally, compound 3 had acceptable metabolic stability. Therefore, compound 3 was merited to further explore for developing a desirable NO donor lead with anti-iCC activity.     

Design and Synthesis of Novel β-Carboline Linked Amide Derivatives as Anticancer Agents

Russian Journal of General Chemistry - A novel series of β-carboline linked amide derivatives is synthesized. The compounds are screened for their anticancer activity against MCF-7 (breast),...     

含硫醚、硒醚及二硫键链接侧链的小檗碱衍生物的合成及体外抗肿瘤活性

为开发高效低毒的抗肿瘤天然产物衍生物,依据药物拼合原理设计并合成了10个新型小檗碱衍生物。将盐酸小檗碱与含单硫醚、单硒醚和二硫键脂肪链片段通过缩合反应得到目标化合物,其化学结构均经过核磁共振氢谱、碳谱以及高分辨质谱确证。采用噻唑蓝（MTT）法考察其体外抗肿瘤活性,结果表明,7个化合物针对不同的癌细胞株的抑制活性优于盐酸小檗碱,同时对人正常肝细胞L02的毒性较低。化合物3e的体外抗肿瘤活性最佳(针对BEL-7402的IC₅₀值为8.70μmol/L,选择性指数为3.61),可对其深入研究用以开发高效低毒的抗肿瘤药物。     

Synthesis of a Regioisomer of β‐Lapachone and Analogs as Potent Antitumor Agents

A regioisomer of β‐lapachone and two analogs were synthesized and evaluated for their antitumor activities. All three compounds tested were found to exhibit promising activities against PC‐3, HepG2, and Raji cancer cell lines in μM range.     

Discovery of Novel Pleuromutilin Derivatives as Potent Antibacterial Agents for the Treatment of MRSA Infection

A series of novel pleuromutilin derivatives containing nitrogen groups on the side chain of C14 were synthesized under mild conditions. Most of the synthesized derivatives displayed potent antibacterial activities. Compound 9 was found to be the most active antibacterial derivative against MRSA (MIC = 0.06 μg/mL). Furthermore, the result of time-kill curves showed that compound 9 had a certain inhibitory effect against MRSA in vitro. Moreover, according to a surface plasmon resonance (SPR) study, compound 9 (K_D = 1.77 × 10⁻⁸ M) showed stronger affinity to the 50S ribosome than tiamulin (K_D = 2.50 × 10⁻⁸ M). The antibacterial activity of compound 9 was further evaluated in an MRSA-infected murine thigh model. Compared to the negative control group, tiamulin reduced MRSA load (~0.7 log₁₀ CFU/mL), and compound 9 performed a treatment effect (~1.3 log₁₀ CFU/mL). In addition, compound 9 was evaluated in CYP450 inhibition assay and showed only moderate in vitro CYP3A4 inhibition (IC₅₀ = 2.92 μg/mL).     

Design,Synthesis, and Evaluation of Novel L-Pyroglutamic Acid Derivatives as Potent Antifungal Agents

Chemistry of Natural Compounds - A series of novel L-pyroglutamate containing 1,2,3-triazole ring substructures was synthesized and characterized by adopting an appropriate synthetic scheme. The...     

Synthesis of New 1, 10‐Phenanthroline Analogs as Potent Antimicrobial Agents Using Montmorillonite K‐10 as Catalyst

A series of new 1, 10‐phenanthroline derivatives are synthesized by the four‐component domino reactions of 8‐hydroxy quinoline, aromatic aldehydes, methyl/ethyl acetoacetate and ammonium acetate in the presence of zeolite (montmorillonite K‐10) using both conventional and microwave methods. Most of the new compounds possessed moderate to significant anti‐bacterial and anti‐fungal activities.     

Synthesis of Some Novel Heterocycles Bearing Thiadiazoles as Potent Anti‐inflammatory and Analgesic Agents

2‐Bromoacetyl‐3‐phenyl‐1,3,4‐thiadiazole derivative was synthesized and reacted with a number of heterocyclic amines to give a series of fused imidazole derivatives. Also, reaction of 2‐bromoacetyl‐3‐phenyl‐1,3,4‐thiadiazole with o‐phenylene diamine and 2‐aminothiophenol yielded the respective products. Moreover, reaction of 2‐bromoacetyl‐3‐phenyl‐1,3,4‐thiadiazole with thiourea, thiosemicarbazide, thiocarbahydrazide gave the respective thiazoles. The structures of all the novel products were elucidated on the basis of elemental analysis and spectral data. In addition, the biological activity of the newly synthesized compounds was evaluated, and the results obtained indicate their potency as anti‐inflammatory, analgesic, and anti‐ulcer agents. The binding mechanism of the most active compounds was studied using MOE to analyze the molecular interactions.     

3D-QSAR of Benzothiazole Derivatives as Potent Anticancer Agents

Comparative molecular field analysis (CoMFA) method was applied to study three-dimensional quantitative structure activity relationship (3D-QSAR) of a series of benzothiazole derivatives as potent anticancer agents. The CoMFA model of cross-validation and the partial-least-square (PLS) model of non cross-validation have been well established. The best CoMFA model gives a good cross-validation coe±cient of 0.642 and a conventional correlation coe±cient of 0.976. Moreover, the estimated standard error is 0.161 and the statistical square deviation ratio F(3;20) is 111.4. The statistical parameters of the best CoMFA model show this model is reasonable and has predictive ability. The CoMFA results suggest that an electron-withdrawing group or atom (e.g. F atom) linking to the first atom (C19) of substituent R can increase the positive charges of C19 and its fi-site atoms, which lie in the blue-colored regions in the electrostatic field contour map of CoMFA, and thus can improve the activity of the compound. Meanwhile, selecting an R with an appropriatevolume is also advantageous for improving the activity.     

Design,Synthesis, and Biological Evaluation of Fluoroquinolones Linked to 4-Thiazolidinone Moieties as Potent Antimicrobial Agents: Docking Analysis

Russian Journal of General Chemistry - A series of novel fluoroquinolone thiazolidinone derivatives were synthesized and evaluated for their biological activity. All the newly synthesized compounds...     

Synthesis,Molecular Docking Studies and In Silico ADMET Screening of New Heterocycles Linked Thiazole Conjugates as Potent Anti-Hepatic Cancer Agents

Thiazoles are important scaffolds in organic chemistry. Biosynthesis of thiazoles is considered to be an excellent target for the design of novel classes of therapeutic agents. In this study, a new series of 2-ethylidenehydrazono-5-arylazothiazoles 5a–d and 2-ethylidenehydrazono-5-arylazo- thiazolones 8a–d were synthesized via the cyclocondensation reaction of the appropriate hydrazonyl halides 4a–d and 7a–d with ethylidene thiosemicarbazide 3, respectively. Furthermore, the thiosemicarbazide derivative 3 was reacted with different bromoacetyl compounds 10–12 to afford the respective thiazole derivatives 13–15. Chemical composition of the novel derivatives was established on bases of their spectral data (FTIR, ¹H-NMR, ¹³C-NMR and mass spectrometry) and microanalytical data. The newly synthesized derivatives were screened for their in vitro anti-hepatic cancer potency using an MTT assay. Moreover, an in silico technique was used to assess the interaction modes of the compounds with the active site of Rho6 protein. The docking studies of the target Rho6 with the newly synthesized fourteen compounds showed good docking scores with acceptable binding interactions. The presented results revealed that the newly synthesized compounds exhibited promising inhibition activity against hepatic cancer cell lines (HepG2).     

Synthesis of Novel Tacrine Analogs as Acetylcholinesterase Inhibitors

In this work, a wide range of novel pyrazolo[4′,3′:5,6]pyrano[2,3‐b ]quinolin‐5‐amines were synthesized as tacrine analogs. At first, reaction of 3‐methyl‐1‐phenyl‐1H‐pyrazol‐5(4H )‐one, aromatic aldehydes, and malononitrile gave 6‐amino‐4‐aryl‐3‐methyl‐1‐phenyl‐1,4‐dihydropyrano[2,3‐c ]pyrazole‐5‐carbonitriles. Then, reaction of the latter compounds with cyclohexanone led to the formation of the title compounds. Also, they were evaluated for their in vitro acetylcholinesterase and butyrylcholinesterase inhibitory activities. Interestingly, most of them showed good inhibitory activity comparing with rivastigmine as the reference drug.     

Deorphaning Pyrrolopyrazines as Potent Multi‐Target Antimalarial Agents

The discovery of pyrrolopyrazines as potent antimalarial agents is presented, with the most effective compounds exhibiting EC₅₀ values in the low nanomolar range against asexual blood stages of Plasmodium falciparum in human red blood cells, and Plasmodium berghei liver schizonts, with negligible HepG2 cytotoxicity. Their potential mode of action is uncovered by predicting macromolecular targets through avant‐garde computer modeling. The consensus prediction method suggested a functional resemblance between ligand binding sites in non‐homologous target proteins, linking the observed parasite elimination to IspD, an enzyme from the non‐mevalonate pathway of isoprenoid biosynthesis, and multi‐kinase inhibition. Further computational analysis suggested essential P. falciparum kinases as likely targets of our lead compound. The results obtained validate our methodology for ligand‐ and structure‐based target prediction, expand the bioinformatics toolbox for proteome mining, and provide unique access to deciphering polypharmacological effects of bioactive chemical agents.     

Synthesis and Evaluation of Pyrazole Derivatives as Potent Antinemic Agents

Russian Journal of Organic Chemistry - Pyrazole derivatives were synthesized by bromination of pyrazole, followed by N-alkylation of 4-bromopyrazole. The synthesized derivatives were characterized...     

5-Phenoxy Primaquine Analogs and the Tetraoxane Hybrid as Antimalarial Agents

The rapid emergence of drug resistance to the current antimalarial agents has led to the urgent need for the discovery of new and effective compounds. In this work, a series of 5-phenoxy primaquine analogs with 8-aminoquinoline core (7a–7h) was synthesized and investigated for their antimalarial activity against Plasmodium falciparum. Most analogs showed improved blood antimalarial activity compared to the original primaquine. To further explore a drug hybrid strategy, a conjugate compound between tetraoxane and the representative 5-phenoxy-primaquine analog 7a was synthesized. In our work, the hybrid compound 12 exhibited almost a 30-fold increase in the blood antimalarial activity (IC₅₀ = 0.38 ± 0.11 μM) compared to that of primaquine, with relatively low toxicity against mammalian cells (SI = 45.61). Furthermore, we found that these 5-phenoxy primaquine analogs and the hybrid exhibit significant heme polymerization inhibition, an activity similar to that of chloroquine, which could contribute to their improved antimalarial activity. The 5-phenoxy primaquine analogs and the tetraoxane hybrid could serve as promising candidates for the further development of antimalarial agents.