|Year : 2019 | Volume
| Issue : 6 | Page : 496-503
Nano-SnCl4.SiO2, an efficient catalyst for synthesis of benzimidazole drivatives as antifungal and cytotoxic agents
Leila Zamani1, Zeinab Faghih1, Kamiar Zomorodian2, Bi Bi Fatemeh Mirjalili3, Asghar Jalilian1, Soghra Khabnadideh1
1 Pharmaceutical Sciences Research Centre, Shiraz University of Medical Sciences, Shiraz, I.R. Iran
2 Center of Basic Researches in Infectious Diseases, Department of Medical Mycology, and Parasitology School of Medicine, Shiraz University of Medical Sciences, Shiraz, I.R. Iran
3 Department of Chemistry, College of Science, Yazd University, Yazd, I.R. Iran
|Date of Web Publication||11-Dec-2019|
Pharmaceutical Sciences Research Centre, Shiraz University of Medical Sciences, Shiraz
Pharmaceutical Sciences Research Centre, Shiraz University of Medical Sciences, Shiraz
Source of Support: None, Conflict of Interest: None
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.
Keywords: Antifungal; Benzimidazole; Cytotoxic; MTT; Nano-SnCl4/SiO2
|How to cite this article:|
Zamani L, Faghih Z, Zomorodian K, Mirjalili BF, Jalilian A, Khabnadideh S. Nano-SnCl4.SiO2, an efficient catalyst for synthesis of benzimidazole drivatives as antifungal and cytotoxic agents. Res Pharma Sci 2019;14:496-503
|How to cite this URL:|
Zamani L, Faghih Z, Zomorodian K, Mirjalili BF, Jalilian A, Khabnadideh S. Nano-SnCl4.SiO2, an efficient catalyst for synthesis of benzimidazole drivatives as antifungal and cytotoxic agents. Res Pharma Sci [serial online] 2019 [cited 2020 Jul 15];14:496-503. Available from: http://www.rpsjournal.net/text.asp?2019/14/6/496/272536
| Introduction|| |
Systemic fungal infections have enlarged in the past few decades, especially in immune-compromised individuals and in organ transplant recipients ,. The expansion of azoles has updated the treatment of many fungal infections, but still treatment of many of them necessitates application of the highly toxic drugs. Emergence of new resistant species of fungi in addition to the poor safety and pharmacokinetics profile, challenges the clinicians in their way to handle the fungal infections . Therefore, an urgent need for new antifungal chemical structures as alternative agents is required. On the other hand, cancer is a major public health problem worldwide . Many publications have shown an increase in the incidence of different type of cancer in the last 40 years .
Several chemotherapeutic agents are now being used to treat human cancers but they have limited success in clinical trials. The main limitations in straight cancer chemotherapy rise from the absence of drug-specific affinity to tumor cells. Thus, there is a critical need to discover novel anticancer agents as well . Benzimidazole is a heterocyclic aromatic molecule with electron rich nitrogen atoms. Its derivatives have many biological applications such as antitumor , antimicrobial , anthelmintic , anti-inflammatory  and anti-diabetic . Different synthetic methods including solid phase synthesis , thermal or acid catalyzed cyclization , ceric ammonium nitrate catalysed  and using of samarium triflate  were reported for synthesis of benzimidazole compounds.
However, some of the above cited methods suffer from several weaknesses like harsh reaction conditions, high catalyst cost, and existence of side reactions or tedious work-up procedure. We also described the synthesis of some benzothiazole , benzoxazine , benzimidazole , tetrazole ,, and benztriazole  derivatives as antifungal agents in our previous studies. Our previous results showed that benzimidazole compounds exhibited favorite biological activities and drug like properties . We also evaluated different type of catalysts for synthesis of azole compounds in our earlier works . Now in continuation of our work here we aimed to use nano-SnCl4.SiO2 as a reusable heterogeneous catalyst for synthesis of 2-substituted benzimidazole compounds with possible antifungal and cytotoxic activities. We also planned to evaluate the antifungal and cytotoxic activities of synthesized compounds. Different species of fungi were chosen for this purpose. In order to identify the potential antitumor candidates, the cytotoxic activities of the potent antifungal compounds were determined against MCF-7 and A549 cell lines.
| Material and Methods|| |
All chemicals were obtained from Merck and Fluka companies (Germany). Fourier-transform infrared attenuated total reflection (FT-IR, ATR) spectra were acquired on a Bruker, Equinox 55 spectrometer (Germany). The proton and carbon-13 nuclear magnetic resonance (1H- and13C-NMR) spectra were run on a DRX-400 Avane (Germany). Melting points were recorded on a Büchi B 545 apparatus (Germany) in open capillary tubes and all are uncorrected.
General procedure for synthesis of benzimidazole derivatives
A mixture of aldehyde (1 mmol), o-phenylenediamine (1 mmol), and nano-SnCl4/SiO2 (0.06 g) were placed in a round bottom flask and heated at 90 °C for 1 h under solvent free condition. Progress of the reaction was followed by thin-layer choromatography (TLC) using EtOAc/n-hexane.
After completion of the reaction, the product was dissolved in chloroform and filtered to recover the catalyst. Then the solvent was evaporated, and the crude mixture was solidified from a mixture of ethanol and water. The pure product was obtained by re-crystallization in ethanol [Scheme 1].
Yellow solid, FT-IR: Vmax (ATR, neat, cm-1): 1462 (C=C stretch), 1277 (C-N bend), 743 and 703 (C-H bend);1H-NMR (400 MHz, DMSO-d6): 7.29 (m, 2H6,5), 7.5 (m, 3H3’,4’,5’), 7.66 (brs, 2H4,7), 8.075 ( dd, J = 7.4, 2 Hz, 2H2’,6’), 10 (brs, 1H, N-H1) ppm.
Yellow crystal, FT-IR: Vmax (ATR, neat, cm-1) = 1429 (C=C stretch), 1273 (C-N bend), 746 (=C-H), cm-1;1H-NMR (400 MHz, CDCl3): 7.32 (brs, 2H6,5), 7.42 (m,3H3’,5’,4), 7.52 (d, J = 7.6 Hz, 1H7), 7.8 (brs, 1H2’), 8.83 (d, J = 7.6 Hz, 1H6’), 10.3 (brs, 1H, N-H1) ppm.
Orange solid, FT-IR: Vmax (ATR, neat, cm-1): 1429 (C=C stretch), 1273 (C-N bend), 746 (=C-H);1H-NMR (400 MHz, CDCl3): 7.32 (brs, 2H6,5), 7.42 (m, 3H3’,5’,4), 7.52 (d, J = 7.6 Hz, 1H7), 7.83 (brs, 1H2’), 8.47 (d, J = 7.6 Hz, 1H6’), 10.3 (brs, 1H, N-H1) ppm.
Yellow solid, FT-IR: Vmax (ATR, neat, cm-1): 1599 (C=N stretch), 1458 (C=C stretch), 1231 (C-N bend), 747 (C-H bend);1H-NMR (400 MHz, DMSO-d6): 7.20 (brs, 2H6,5), 7.6 (brs, 2H3’,5’), 7.8 (d, J = 7.2 Hz, 2H4,7), 8.1 (d, J = 7.2 Hz, 2H2’,6’), 13.1 (s, 1H, N-H1) ppm.
2 - (2’, 3’- Dihydroxyphenyl) - 1 H - benz- imidazole (J5)
Red crystal; FT-IR: Vmax (KBR, cm-1) = 3453 (O-H), 1618 (C=N stretch), 1580 (C=C stretch), 1543 (N-H bend), 1460 (C=C stretch), 1210 (C-N bend), 1032 (C-H bend), 763 (C-H bend);1H-NMR (400 MHz, DMSO-d6): 6.77 (t, J = 7.6 Hz, 1H5’), 6.92 (d, J = 6.4 Hz, 1H4’), 7.095 (d, J = 6.4 Hz, 1H6’), 7.4 (brs, 4H4, 5, 6, 7), 8.86 (s, O-H2), 9.27 (s, O-H3’), 12.91 (s, 1H, N-H1) ppm.
2 - ( 4 '- Nitrophenyl )- 1 H - 5 - methyl - benz- imidazole (J6)
Yellow crystal; FT-IR: Vmax (KBR, cm-1) = 1603 (C=N stretch), 1520 (NO2 stretch), 1344 (NO2 stretch), 1109 (C-N bend) cm-1,1H NMR (400 MHz, DMSO-d6): 2.43 (s, 3Hmethyl), 7.1 (s, 1H7), 7.4-7.6 (m, 2H4,6), 8.4 (m, 4H2’,3’,5’,6’), 13.3 (s, 1H, NH1) ppm.
2 - ( 4’ - Nitrophenyl) - 1 H - 5 - nitro - ben z- imidazole (J7)
Orange crystal; FT-IR: Vmax (KBr, cm-1) = 1605 (C=N stretch), 1522 (NO2 stretch), 1418 (C=C stretch), 1344 (NO2 stretch), 759 (C-H bend) cm-1;1H NMR (400 MHz, DMSO-d6): 7.80 (brs, 1H7), 8.12 (brs, 1H4), 8.41 (brs, 4H6,2’,6’,3’), 8.49 (brs, 1H5’), 13.9 (s, 1H, N-H1) ppm.
Red solid; FT-IR: Vmax (KBr, cm-1) = 3160 (=C-H stretch), 1600 (C=N stretch), 1575 (C-N bend) cm-1;1H NMR (400 MHz, DMSO-d6): 3.15-3.55 (m, 4Hethyl), 6.5-7.8 (m, 9H2’,3’,4’,5’,6’, 4, 5, 6, 7, and 1H, N-H1) ppm.
2-(2’,3’-Dihydroxyphenyl)-1H-5-nitro-benz- imidazole (J9)
Red solid, FT-IR: Vmax (ATR, neat, cm-1): 3391 (O-H), 1603(C=N stretch), 1459 (C=C stretch), 1338 (NO2 stretch), 1264 (C-N bend);1H-NMR (400 MHz, (CD3)2CO): 6.9 (t, J = 7.6 Hz, 1H4’), 6.98 (d, J = 8.8 Hz, 1H5’), 7.04 (d, J = 7.6 Hz, 1H6’), 7.2 (d, J = 7.6 Hz, 1H7), 7.8 (s, 1H4), 7.9 (d, J = 8.4, 1H6), 8.04 (s, O-H), 8.9 (s, O-H), 12.5 (s, 1H,N-H1) ppm.
2 - (4’ - Hydroxyphenyl) - 1 H5 - nitro - benz- imidazole (J10)
Yellow solid, FT-IR: Vmax (ATR, neat, cm-1): 3401 (O-H stretch), 1609 (C=N stretch), 1425 (C=C stretch), 1126 (C-N bend), 758 (C-H bend);1H NMR (DMSO-d6): δ 3.5 (br s, O-H), 6.9 (d, J = 8.4 Hz, 2H3’,5’), 7.38(m, 2H4,7), 7.51(m, 2H4,7), 7.98 (d, J = 8.4 Hz, 2H2’,6’), 9.98 (s, 1H, N-H1) ppm.
The antifungal activities of the synthesized compounds were examined against some American type culture collection (ATCC) strains of fungi including Candida albicans (C. albicans, ATCC 10261), C. dubliniensis (CBS 8501), C. parapsilosis (ATCC 4344), C. krusei (ATCC 6258), C. tropicalis (ATCC 750), Cryptococcus neoformanse (H99), Aspergillus flavus (ATCC 64025), Aspergillus clavatus (CBS 514.65), Alternaría alternate, Microsporum canis, and Trichophyton mentagrophytes. The susceptibility of all clinical isolates of fungi against selected antibiotics was examined by microdilution and disk diffusion methods.
Determination of minimum inhibitory concentration
Minimum inhibitory concentrations (MICs) were determined using the broth micro dilution method recommended by the clinical and laboratory standard institute. Briefly, for determination of antimicrobial activities against fungi, serial dilutions of the synthesized compounds (J1-J10) were prepared in 96-well micro titer plates using RPMI-1640 media buffered with 3-(N-morpholino)propanesulfonic acid (MOPS). Stock inoculums were prepared by suspending three colonies of the examined yeast in 5 mL sterile 0.85% NaCl, and adjusting the turbidity of the inoculums to 0.5 McFarland standards at 530 nm wavelengths. For molds, conidia were recovered from the 7-day old cultures grown on potato dextrose agar by a wetting loop with Tween20. The collected conidia were transferred in sterile saline and their turbidity was adjusted to 0.09-0.11 optical density. Working suspension was prepared by making a 1:50 and 1:1000 dilution with RPMI of the stock suspension for molds and yeasts, respectively. Working inoculums were added to the micro titer plates and incubated in a humid atmosphere at 30 °C for 24-48 h. Inoculated medium was included as a sterile control. In addition, growth controls (medium with inoculums but without antibiotics or the synthetic compounds) were also included. The growth in each well was compared with that of the growth in the control well. Fluconazole was used as positive control.
Cell lines and cell culture
Two human cancer cell lines, MCF-7 and A549, were purchased from the National Cell Bank of Pasteur Institute of Iran. Using aseptic techniques, the cells were cultured in RPMI 1640 medium, containing 10% fetal bovine serum, 100 penicillin, streptomycin (100 μg/mL), and incubated at 37 °C in a humidified atmosphere with 5% CO2. Following enough confluence, the cells were treated with 25% trypsin-EDTA and sub-cultured. The cells were then washed, counted, and prepared for cytotoxic MTT assay as previously described ,,.
More active benzimidazole compounds (J2, J5-J7) according to antifungal studies were chosen for cytotoxic evaluation. Briefly 104 cells in the complete culture medium were seeded per well in a 96-well cell culture microplate. After attachment the cells were treated with different concentrations of each compound (1-1000 μM). Three wells were left without treatment as cell-based negative controls, and three wells containing cell culture medium alone were considered as blanks. Cisplatin was used as positive control. After 48 h incubation, the culture media were removed and 100 μL of MTT solution (0.5 mg/mL) were added to the wells including controls. The plate was incubated for 3-4 h at 37 °C and checked periodically for the appearance of purple precipitate. After complete removing of MTT solution, 150 μL of DMSO was added to the wells and left in the 37 °C incubator for more 30 min. The absorbance of all wells including the blanks, were measured at 570 nm. The optical density (OD) of individual well was obtained at 570 nm using a microplate ELISA reader (Biotek, USA). Data are presented as mean ± SD of three separate experiments.
The average values from triplicate readings were determined and subtracted the average value for the blank. The inhibitory concentration (IC) of each compound was calculated and reported using following equation:
For each chemical a plot of the IC versus concentration was depicted using Curve Expert 1.4 software and IC50 was obtained for each compound. P values less than 0.05 were considered statistically significant.
| Results|| |
Ten 2-substituted benzimidazole analogs were synthesized in the presence of nano-SnCl4.SiO2 under solvent free conditions. All synthesized compounds and their characteristics are shown in [Table 1].
Antifungal activities of the synthetic compounds
[Table 2] summarizes the inhibitory activities of the synthetic compounds against the tested fungi. MIC values of the synthetic compounds indicated that J2 exhibited strong inhibitory activities against most of the tested fungi. Compounds J5 and J6 showed their greatest inhibitory activities against C. krusei and C. dubliniensis at 32 and 64 μg/mL, respectively. Compounds J7 showed moderate inhibitory activity against C. dubliniensis, C. krusei, and C. neoformance.
|Table 2: Minimum inhibitory and fungicidal concentrations (μg/mL) of the synthesized compounds against examined fungi.|
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The cytotoxic activities of J2, J5-J7 were investigated against MCF-7 and A549 cells. The IC50 values of tested compounds are presented in [Table 3]. J2 was found as the most active compounds which exhibited higher toxicities with IC50 of 127.2 ± 4.6 and 157.55 ± 5.3 μM against MCF-7 and A549 cell lines respectively. J5 and J6 with IC50 values of 656.4 ± 10.8 and 590.12 ± 2.2 μM for MCF-7 and 254.2 ± 9.6 and 635.65 ± 1.9 μM for A549 cell lines showed moderate to weak cancer cell toxicity. J7, however, showed no cytotoxic effects against investigated cell lines.
|Table 3: In vitro cytotoxicity (IC50, μM) of four investigated benzimidazole on two different cancer cell lines.|
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| Discussion|| |
Solid acids do less harm to the environment and have many advantages over liquid acids  . We demonstrated a simple method for synthesis of azole compounds as possible biologically active compounds. Benzimidazoles are important class of heterocyclic compounds which have a wide range of therapeutic effects such as antimicrobial, antiviral, antifungal, antihypertension, and anticancer activities
 . Synthesized benzimidazoles exhibited wide range of antifungal activities. Substitution of chloro, trifluoromethyl, methoxy, and ethoxy groups at 5 position were found to be more potent substituents . A highly efficient method for the synthesis of benzimidazole analogues was developed by treatment of o-phenylenediamine with aldehyde moiety. We used nano-SnCl4.SiO2 as eco-friendly and efficient catalyst in a one-pot procedure. Short reaction time, high yield, clean and simple procedure, easy work-up, and green condition are advantages of this protocol. The lower cost of the catalyst and the utilization of environmental protection are the other benefits of this method. Ten derivatives were synthesized and characterized by different spectroscopic methods. Different aldehydes were used to create the benzimidazole ring and also put the desired substitution at the 2 position of the ring. Compounds J2 as the most potent compound, showed antifungal activity against C. neoformans, C. krusei, C. dubliniensis, Microsporum canis, C. albicans, at 8-64 μg/mL. The cytotoxic activities of four derivatives (J2, J5-J7) were also assessed against two cancerous cell lines. Similar to antifungal results, J2 had satisfactory anti-tumour activities especially on breast cancer cell line (MCF-7) compared to carcinoma cell line (A549). Compounds J5 and J6 had also moderate activities while J7 showed no toxicities. This activity may be related to chemical structure of the compounds. As it is observed in [Table 1], the presence of small electronegative halogen group (fluorine) in J2 structure at para position of the benzene ring increased the cytotoxic activities.
| Conclusion|| |
Recently, the emphasis on green chemical principles introduced some significant advances in organic synthesis. In this regard, heterogeneous catalysts have found considerable interest in organic reactions. Reactions with these catalysts are generally clean and selective and give high yields of products . Our results collectively indicated that nano-SnCl4.SiO2 was a mild and cost-effectiveness catalyst for synthesis of benzimidazole compounds. Among our synthesized compounds, J2 showed antifungal activity against different fungi species at lower concentration. Based on the cytotoxic effects of potent antifungal derivatives, J2 also had reasonable antitumor activities on both examined cancerous cell lines. Our data suggest that among these analogues of benzimidazoles, J2, with the highest potency on both antifungal and cytotoxic tests, could be introduced as a proper candidate for further in vitro and in vivo studies.
| Acknowledgments|| |
This work was financially supported by Shiraz University of Medical Sciences, Shiraz, I.R. under the Grant No. 93-01-05-7697.
| References|| |
Eggimann P, Garbino J, Pittet D. Epidemiology of Candida
species infections in critically ill non-immunosuppressed patients. Lancet Infect Dis. 2003 ;3(11):685-702.
Caston-Osorio JJ, Rivero A, Torre-Cisneros J. Epidemiology of invasive fungal infection. Int J Antimicrob Agents. 2008;32 (Suppl 2):S103-S109.
Karami B, Khodabakhshi S, Hashemi F. Synthesis of a novel class of benzofurans via a three-component, regiospecific intramolecular heterocylization reaction. Tetrahedron Letters. 2013;54(28):3583-3585.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11-30.
Huyghe E, Matsuda T, Thonneau P. Increasing incidence of testicular cancer worldwide: a review. J Urol. 2003;170(1):5-11.
Rahmannejadi N, Zomorodian K, Faghih Z, Faghih Z, Khabnadideh S, Yavari I. Preparation, docking, antimicrobial and cytotoxic activities of 2-arylquinazolinones. J Pharm Res Int. 2017;20(3):1-11.
Ates-Alagoz Z. Antimicrobial activities of 1-H-benzimidazole-based molecules. Curr Top Med Chem. 2016;16(26):2953-2962.
El-masry A, Fahmy H, Ali Abdelwahed S. Synthesis and antimicrobial activity of some new benzimidazole derivatives. Molecules. 2000;5(12):1429-1438.
Tahlan S, Kumar S, Narasimhan B. Pharmacological significance of heterocyclic 1H-benzimidazole scaffolds: a review. BMC Chem. 2019;13(101):1-21.
Achar KC, Hosamani KM, Seetharamareddy HR. In-vivo
analgesic and anti-inflammatory activities of newly synthesized benzimidazole derivatives. Eur J Med Chem. 2010;45(5):2048-2054.
Walia R, Hedaitullah M, Naaz SF, Iqbal K, Lamba HS. Benzimidazole derivatives - an overview. Int J Res Pharm Chem. 2011;1(3):565-574.
Biron E, Chatterjee J, Kessler H. Solid-phase synthesis of 1, 3-azole-based peptides and peptidomimetics. Org Lett. 2006;8(11):2417-2420.
Benincori T, Sannicolo F. New benzimidazole synthesis. J Heterocycl Chem. 1988;25(3): 1029-1033.
Sadek KU, Al-Qalaf F, Mekheimer RA, Elnagdi MH. Cerium (IV) ammonium nitrate-mediated reactions: Simple route to benzimidazole derivatives. Arab J Chem. 2012;5(1),63-66.
Narsaiah AV, Reddy AR, Yadav J. Mild and highly efficient protocol for the synthesis of benzimidazoles using samarium triflate [Sm(OTf)3
]. Synth Commun. 2010;41(2):262-267.
Mirjalili BBF, Kabnadideh S, Zomorodian K, Zamani L, Faghih M, Haghighijoo Z, et al
. Synthesis, docking study and antifungal activity evaluation of some 1, 3-benzo [d] thiazole analogs: a promotion in synthetic method with nano-gamma- Al2O3/BF3-n
under solvent free conditions. J Pharm Res Int. 2017;19(2):1-26.
Zamani L, Khabnadideh S, Zomorodian K, Sakhteman A, Gholami A, Rezaei Z, et al
. Docking, synthesis, antifungal and cytotoxic activities of some novel substituted 4 H-benzoxazin-3-one. Polycycl Aromat Compd. 2019;1-21.
Khabnadideh S, Rezaei Z, Pakshir K, Zomorodian K, Ghafari N. Synthesis and antifungal activity of benzimidazole, benzotriazole and aminothiazole derivatives. Res Pharm Sci. 2012;7(2):65-72.
Momenzadeh M, Jamshidzadeh A, Khabnadideh S, RezaHeidari UN, Zamani L. Synthesis and anticonvulsant activity of 5-substituted 1h-tetrazoles against pentylenetetrazole-induced seizures. Int. J Adv Biotechnol Res. 2017;8(2):1144-1153.
Zamani L, Mirjailli BBF, Zomorodian K, Zomorodian S. Synthesis and characterization of 5-substituted 1 H-tetrazoles in the presence of nano- TiCl4. SiO2. S Afr J Chem. 2015;68(1):133-137.
Rezaei Z, Khabnadideh S, Pakshir K, Hossaini Z, Amiri F, Assadpour E. Design, synthesis, and antifungal activity of triazole and benzotriazole derivatives. Eur J Med Chem. 2009;44(7): 3064-3067.
Zomorodian K, Khabnadideh S, Zamani L, Pakshir K, Tajaddod M. Evaluation of antifungal and antibacterial activity of some new benzimidazole derivatives. Lat Am Res Rev. 2018;48:125-129.
Zamani L, Mirjalili BBF, Zomorodian K, Namazian M, Khabnadideh S, Faghih Mirzaei E. Synthesis of benzimidazoles in the presence of nano-TiCl4. SiO2 as antifungal agents and tautomerism theoretical study of some products. Farmacia. 2014;62(3):467.
Fereidoonnezhad M, Shahsavari HR, Lotfi E, Babaghasabha M, Fakhri M, Faghih Z, et al
. (Benzyl isocyanide) gold (I) pyrimidine-2-thiolate complex: Synthesis and biological activity. Appl Organomet Chem. 2018;32(3):e4200.
Faghih Z, Neshat A, Wojtczak A, Faghih Z, Mohammadi Z, Varestan S. Palladium (II) complexes based on Schiff base ligands derived from ortho-vanillin; synthesis, characterization and cytotoxic studies. Inorganica Chim Acta. 2018;471:404-412.
Faghih Z, Rahmannejadi N, Sabet R, Zomorodian K, Asad M, Khabnadideh S. Synthesis of some novel dibromo-2-arylquinazolinone derivatives as cytotoxic agents. Res Pharm Sci. 2019;14(2): 115-121.
Mirjalili B, Bamoniri A, Mirhoseini M. Nano-SnCl4 · SiO2: An efficient catalyst for one-pot synthesis of 2, 4, 5-tri substituted imidazoles under solvent-free conditions. Sci Iran. 2013;20(3):587-591.
Taherian E, Khodarahmi G, Khajouei MR, Hassanzadeh F, Dana N. Synthesis and cytotoxic evaluation of novel quinozalinone derivatives with substituted benzimidazole in position 3. Res Pharm Sci. 2019;14(3):247-254.
Küçükbay H, Durmaz R, Orhan E, Günal S. Synthesis, antibacterial and antifungal activities of electron-rich olefins derived benzimidazole compounds. Farmaco. 2003;58(6):431-437.
Hakimi AM, Lashgari N, Mahernia S, Ziarani GM, Amanlou M. Facile one-pot four-component synthesis of 3,4-dihydro-2-pyridone derivatives: novel urease inhibitor scaffold. Res Pharm Sci. 2017;12(5):353-363.
[Table 1], [Table 2], [Table 3]