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Oxindoles and spirooxindoles as poly-functionalized heterocycles are important synthetic targets because of their biological activity and applications to pharmaceutical guide discovery. The spirooxindole structure is usually found in a variety of complex alkaloids and many compounds that possess biological activity. In this study, we have proposed an easy and efficient access to spirooxindole from N-alkylated isatin derivatives, an activated methylene and 4-hydroxycumarin to get such compounds powerfully and suitably. Here we synthesized 18 new derivatives (4a–4r) of spirooxindoles by multicomponent reaction method. Chemical structures of all products were confirmed by IR, 1HNMR, 13CNMR, and Mass Spectroscopy. The reaction conditions were also optimized in the point of different kinds of catalysts, temperature, and solvents. [ABSTRACT FROM AUTHOR]

Background and purpose: Synthesis and investigation of pharmacological activity of novel compounds are time and money-consuming. However, computational techniques, docking, and in silico studies have facilitated drug discovery research to design pharmacologically effective compounds. Experimental approach: In this study, a series of quinazoline derivatives were applied to quantitative structure-activity relationship (QSAR) analysis. A collection of chemometric methods were conducted to provide relations between structural features and cytotoxic activity of a variety of quinazoline derivatives against breast cancer cell line. An in silico-screening was accomplished and new impressive lead compounds were designed to target the epidermal growth factor receptor (EGFR)-active site based on a new structural pattern. Molecular docking was performed to delve into the interactions, free binding energy, and molecular binding mode of the compounds against the EGFR target. Findings/Results: A comparison between different methods significantly indicated that genetic algorithm-partial least-squares were selected as the best model for quinazoline derivatives. In the current study, constitutional, functional, chemical, resource description framework, 2D autocorrelation, and charge descriptors were considered as significant parameters for the prediction of anticancer activity of quinazoline derivatives. In silico screening was employed to discover new compounds with good potential as anticancer agents and suggested to be synthesized. Also, the binding energy of docking simulation showed desired correlation with QSAR and experimental data. Conclusion and implications: The results showed good accordance between binding energy and QSAR results. Compounds Q1-Q30 are desired to be synthesized and applied to in vitro evaluation. [ABSTRACT FROM AUTHOR]

A series of some novel 4H-benzoxazin-3-one derivative (1a-20a) was designed, synthesized and evaluated as antifungal and anticancer agents. Benzoxazine compounds were synthesized in only two steps. In the first step, o-aminophenols derivatives reacted with chloroacetyl chloride in the presence of K2CO3 to produce a 4H-benzoxazin-3-one intermediate. In the second step, this intermediate was reacted to various alkyl or aryl halides to get the final products. Then, the synthetic benzoxazine compounds were evaluated for their antifungal activity against different species of fungi. Compound 13a MICs GM of 28.5 µg/mL and then compounds 14a, 17a with MICs GM of 47.2 and 50.7 µg/mL demonstrated the most excellent inhibitory activities against Candida strains, respectively. In addition, the potential cytotoxic activities of all compounds were evaluated by two methods: MTT test, and also lactate dehydrogenase test (LDH). According to the biological results, the most of our compounds especially those containing benzyl groups on the nitrogen atom showed significant antifungal activity. Cytotoxic activities of the compounds were also determined on Hep-G2 and SW cell lines by MTT method and LDH. In MTT assay, compounds 5a, 6a and 8a showed the best results (IC50: 3.12 µg/mL) followed by compounds 7a, 13a and 17a (IC50: 6.25 µg/mL) on the Hep-G2 cells. The best cytotoxic compounds against SW cells were 17a and 18a. The LDH assay showed the same results with MTT of SW. [ABSTRACT FROM AUTHOR]

Two novel series of quinazolinone–pyrimidine (series a: 9a–9i) and benzyl-pyrimidine hybrids (series b: 12a–12c) were designed, synthesized and characterized by spectroscopic methods. The dipeptidyl peptidase-4 inhibition potencies of these compounds were assessed through a MAK 203 kit. Compound 9e was found to be the most potent agent with an IC50 value of 34.3 ± 3.3 μM. A kinetic study revealed that it acted as a competitive inhibitor. Molecular modeling of these compounds was in agreement with the in vitro results. Due to the crucial role of dipeptidyl peptidase-4 in cancer therapy, the cytotoxic activities of the compounds were also evaluated against three cancerous cell lines (HT-29, SW1116 and A549). Almost all the compounds displayed better antiproliferative activity on colon cancer cell lines (HT-29 and SW1116) compared to a lung cancer cell line (A549). Compounds 9e and 12c exhibited significant activity toward the HT-29 cell line with an IC50 of 10.67 ± 0.3 μM and 27.9 ± 6.5 μM in comparison to sitagliptin and cisplatin as a positive control, respectively. Among the different cells, the compounds showed the best inhibitory effects on HT-29, which was compatible with the greater expression of the dipeptidyl peptidase-4 marker detected by flow cytometry in this cell line. Further studies on the hit compounds (9e and 12c) through cell cycle and apoptosis assays also showed that these compounds could induce cell death by apoptosis or arrest cells in the G2/M phase. Accordingly, the results imply that 9e is a potent inhibitor of dipeptidyl peptidase-4 with efficient anti-cancer activity and could play a role as a cytotoxic agent in colorectal cancer. [ABSTRACT FROM AUTHOR]

Owing to the wide applications and significance of phloroglucide analogues in organic synthesis, pharmacology and industry, there is considerable interest in the synthesis of these compounds. Nevertheless, there are few methods for preparation of these compounds. Here we reported a simple, clean, and highly efficient procedure for the green synthesis of tricyclic polyhydroxyl aromatic compounds. Microwave-assisted alkylation reaction between 4-substituted-2, 6-bis(chloromethyl)phenols and various phenol derivatives, in the presence of zinc oxide (ZnO) in 1-butyl-3-methylimidazolium hexaflourophosphate ([Bmim]PF6), affords the title compounds in short duration with high yields. We have synthesized 18 derivatives of the title compounds 3a-3r by this procedure. Chemical structures of all synthesized compounds have been confirmed by spectrophotometric methods such as IR, NMR and mass spectroscopy. Some of the synthesized compounds have been screened for their antimicrobial activities. Antifungal and antibacterial activities have been evaluated against different species of microorganisms including gram positive and gram negative bacteria as well as fungi. Broth microdilution method as recommended by Clinical and Laboratory Standard Institute has been used for this purpose. The results show compounds 3i, 3k and 3m have the best antibacterial and antifungal activity against most of the examined species. Compounds 3b, 3f, 3o, 3p and 3q also show good activity against some species. [ABSTRACT FROM AUTHOR]

The extensive use of antimicrobial drugs and their resistance against bacterial infections have led to discover new antimicrobial compounds. In this study, we wish to report, one-pot synthesis of 2-amino-3- cyanopyridine derivatives (1a-14a). These compounds were synthesized in the presence of Cu(OAc)2 as a highly effective heterogeneous acid catalyst. Here we evaluated the antimicrobial activities of these compounds against different species of microorganisms including gram positive and gram negative bacteria as well as fungi. Standard antimicrobial methods include disc diffusion and Broth microdilution method according to the protocol of the Clinical and Laboratory Standards Institute (CLSI). Synthesis of 2-amino-3-cyanopyridine derivatives were done via reaction of aromatic aldehydes, acetophenone derivatives, malononitrile and ammonium acetate in the presence of Cu(OAc)2 under reflux condition. The results show compound 2-amino-6-(4-chlorophenyl)-4- phenylnicotinonitrile (10a) had the best antimicrobial efficacy toward C. albicans, E. faecalis, P. aeroginosa and E. coli. In conclusion, comparing the structure and activity of the compounds (10a), this compound with the presence of Cl residue at para-position of phenyl ring improves the antibacterial and antifungal activity. [ABSTRACT FROM AUTHOR]

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The concept of green chemistry has made significant impact on many frontages including the use of green solvents or sustainable catalyst materials. Benzimidazole ring is an important nitrogen-containing heterocyclic, which exhibits a broad spectrum of bioactivities and are widely utilized by the medicinal chemists for drug discovery. A simple and efficient method was developed for the synthesis of some benzimidazole derivatives via reaction of o-phenylenediamine and substituted aldehydes in the presence of nano-SnCl4/SiO2 as a mild catalyst. Ten 2-substituted benzimidazole compounds (J1-J10) were synthesized. All compounds were evaluated against different species of yeasts and filament fungi using broth micro dilution method as recommended by clinical and laboratory standard institute. Among these compounds, the active ones were chosen for their cytotoxic activities evaluation against MCF-7 and A549 cell lines using MTT method. Compound J2 showed the best antifungal activity against all tested species. Compounds J5-J7 had also desirable antifungal activities. Our cytotoxic results were also similar to the antifungal activities except for J7 which had no cytotoxic activity. [ABSTRACT FROM AUTHOR]

Recently the quinazoline derivatives have attracted much attention for their anticancer properties. In this study a series of new brominated quinazoline derivatives (1a-1g) were synthesized in two steps. In the first step we used N-bromosuccinimide to brominate the anthranilamid. Then in the second step we closed the quinazoline ring by different aromatic aldehydes. Our aldehydes contain different electron donating or electron withdrawing groups at different positions of the aromatic ring. The chemical structures of products were confirmed by spectroscopic methods such as IR, 1HNMR, 13CNMR, and mass spectroscopy. The cytotoxic activities of the compounds were assessed on three cancerous cell lines including MCF-7, A549, and SKOV3 using colorimetric MTT cytotoxic assay in comparison with cisplatin as a standard drug. Our results collectively indicated that 1f and 1g, exhibited the best anti-proliferative activities on three investigated cancerous cell lines. [ABSTRACT FROM AUTHOR]

Quinazoline is one of the most widespread scaffolds amongst natural and synthetic bioactive compounds. Recently the quinazoline derivatives and in particular the 4-anilinoquinazolines have attracted much attention for their anticancer properties due to their capability to stabilize the kinase activity of epidermal growth factor receptor (EGFR). A series of fifteen previously designed and synthesized 4-anilinoquinazoline analogs (4-18) were evaluated for cytotoxic activity on two breast cancer cell lines (MCF-7 and MDA-MB-468). Ligand efficiency and binding mode studies were also done and evaluated for their potentially EGFR inhibitory effects in comparison with imatinib and erlotinib as reference drugs. Among the tested 4-anilinoquinazolines, compound 11, which contains diethoxy at phenyl ring and morpholino pendants at positions 5 and 7 of the quinazoline ring, demonstrated the most potent biological activity on both cell lines. Our new quinazoline derivatives with different substituents such as cyclic or linear ethers and flour groups may be a promising cytotoxic lead compounds for further anti-breast cancer research. [ABSTRACT FROM AUTHOR]

Aromatase inhibitors (AIs) as effective candidates have been used in the treatment of hormone-dependent breast cancer. In this study, we have proposed 300 structures as potential AIs and filtered them by Lipinski's rule of five using DrugLito software. Subsequently, they were subjected to docking simulation studies to select the top 20 compounds based on their Gibbs free energy changes and also to perform more studies on the protein-ligand interaction fingerprint by AuposSOM software. In this stage, anastrozole and letrozole were used as positive control to compare their interaction fingerprint patterns with our proposed structures. Finally, based on the binding energy values, one active structure (ligand 15) was selected for molecular dynamic simulation in order to get information for the binding mode of these ligands within the enzyme cavity. The triazole of ligand 15 pointed to HEM group in aromatase active site and coordinated to Fe of HEM through its N4 atom. In addition, two p-cation interactions was also observed, one interaction between triazole and porphyrin of HEM group, and the other was 4-chloro phenyl moiety of this ligand with Arg115 residue. [ABSTRACT FROM AUTHOR]

Background: α-Aminophosphonates are bioisosters of amino acids and have several pharmacological effects. α-Aminophosphonates have been synthesized by various routes from reaction between an amine, an aldehyde, and phosphate compounds. Materials and Methods: We synthesized 20 new α-aminophosphonates in the presence of FeCl3 in THF as a catalyst to facilitate the Manich-type reaction of aldehyde, amine and phosphite compounds to form the corresponding α-aminophosphonates in a one-pot, three-component reaction. In this study, the catalytic effect of ZnCl2 was also compared with FeCl3 in the synthesis of α-aminophosphonates. Results: The results showed that FeCl3 catalyzed the reaction in mild conditions to form α-aminophosphonates with high yields, but ZnCl2 did not give high yields of the compounds and the reaction took longer time in comparison to that taken by FeCl3 The chemical structures of all new compounds were confirmed by spectrophotometric methods (1HNMR, 13CNMR, IR). The compounds were investigated for antimicrobial activity against Escherichia coli, Bacillus subtilis, Salmonella typhi, Shigella sonnei, Proteus vulgaris, and Staphylococcus epidermidis. Conclusion: The new synthesized compounds did not show good antibacterial activity against the tested microorganisms. [ABSTRACT FROM AUTHOR]

Carbamazepine (CBZ) and phenytoin (PHT) are two antiepileptic drugs which are used simultaneously. In this paper a partial least-squares (PLS) calibration method is described for the simultaneous spectrophotometric determination of CBZ and PHT in plasma. Standard binary mixtures of CBZ and PHT have been resolved by application of PLS-1 to their UV spectra. Then, the binary standard solutions, spiked to plasma, were prepared and after the extraction of the drugs, their corresponding UV spectrum were analyzed by PLS regression to calculate the concentration of drugs in unknown plasma. A leave one out cross-validation procedure was employed to find the optimum numbers of latent variables using PRESS. A HPLC method was also applied for simultaneous determination of two drugs in the plasma and in methanol. The mean recoveries obtained by PLS were 98.4 and 98.2 for CBZ and PHT and those obtained by HPLC were 100.1 and 101.7, respectively. Although, the HPLC method showed better performance than PLS, it was found that the results obtained by PLS were comparable with those obtained by HPLC method. [Copyright &y& Elsevier]

Diaper dermatitis is a common disorder. Coriandrum sativum is a herbal remedy with anti-inflammatory, analgesic, anti-microbial and anti-oxidant activities effects. In this non- randomised clinical trial which was performed on 58 infants with diaper dermatitis referred to Faghihi Hospital, Shiraz University of Medical Sciences, the efficacy and safety of topical Coriandrum extract cream is compared with hydrocortisone ointment. Coriandrum sativum extract cream was administered for 37 (intervention group) and hydrocortisone 1% ointment for 21 (control group) patients. Patients were examined on days 3 and 10. Chi-square test was applied for statistical analysis. The results demonstrated a statistically significant difference in the cure rate (20 (54.1%) for the intervention group versus 19 (90.5%) for the control group) (P-value = 0.005) and side effects (10 (27%) for the intervention group versus 0 (0%) for control group) (P-value = 0.009) both in favor of hydrocortisone. This trial failed to confirm the efficacy of Coriandrum sativum in the treatment of diaper dermatitis; however, it seems that if soothing compounds are used in combination with Coriandrum sativum to reduce the mild irritation, Coriandrum extract can be an alternative treatment for diaper dermatitis. [ABSTRACT FROM AUTHOR]

Background: Azoles are the famous and widespread scaffold in the pharmaceutical industry due to their wide range of activities, high efficacy, good tolerability, and oral availability. Furthermore, azole derivatives have attracted attention as potent antimicrobial agents., Introduction: The purpose of this review is to provide an overview of pharmacological aspects of the main scaffolds of azoles, including imidazole, benzimidazole, triazole, and tetrazole, which possess antimicrobial activity, reported from 2016 to 2020, as well as all of our publication in this field. In addition, we discuss the relationship between structure and activity and molecular docking studies of the azole derivatives to provide critical features and valuable information for the synthesis of novel azole compounds with desirable biological activities. The presented structures in this review have been tested against several bacteria and fungi, such as E. coli and C. albicans, which have been common in all of these studies., Results: A comparison of the reported MIC for tested compounds showed fluconazole base structures as the most active antifungal agents, and triazole derivatives bearing nitrophenyl and coumarin moieties to have the most dominant antibacterial activity., Conclusion: Triazole and imidazole scaffolds are more important for designing antimicrobial compounds than other azole derivatives, like benzimidazole or tetrazole. All the most active compounds were observed to fulfill the Lipinski rule., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The concept of green chemistry has made significant impact on many frontages including the use of green solvents or sustainable catalyst materials. Benzimidazole ring is an important nitrogen-containing heterocyclic, which exhibits a broad spectrum of bioactivities and are widely utilized by the medicinal chemists for drug discovery. A simple and efficient method was developed for the synthesis of some benzimidazole derivatives via reaction of o -phenylenediamine and substituted aldehydes in the presence of nano-SnCl 4 /SiO 2 as a mild catalyst. Ten 2-substituted benzimidazole compounds ( J 1 -J 10 ) were synthesized. All compounds were evaluated against different species of yeasts and filament fungi using broth micro dilution method as recommended by clinical and laboratory standard institute. Among these compounds, the active ones were chosen for their cytotoxic activities evaluation against MCF-7 and A549 cell lines using MTT method. Compound J 2 showed the best antifungal activity against all tested species. Compounds J 5 -J 7 had also desirable antifungal activities. Our cytotoxic results were also similar to the antifungal activities except for J 7 which had no cytotoxic activity., (Copyright: © 2019 Research in Pharmaceutical Sciences.)