International Journal of Advanced and Applied Sciences, 7(2) 2020, Pages: 69-77 Contents lists available at Science-Gate International Journal of Advanced and Applied Sciences Journal homepage: http://www.science-gate.com/IJAAS.html Evaluation of some new synthesis benzothiazole and benzimidazole derivatives as potential antimicrobial and anticancer agents Amani Abd Elrazig Salman Abd Elaziz 1, *, Ahmed M. Farag 2, Ishraga Izzeldin Abdelrahim Alagib 1, Emad M. Abdallah 3, Nawadir Eltieb Abdlla Mohammed 1 1Department of Basic Science (Chemistry), Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia 2Department of Chemistry, Faculty of Science, Cairo University, Giza, Egypt 3Department of Laboratory Sciences, College of Sciences and Arts, Qassim University, Al-Rass, Saudi Arabia ARTICLE INFO ABSTRACT Article history: There is an urgent global need to develop new antimicrobial and anti-cancer Received 15 September 2019 drugs. In the current study, the biological evaluation of some synthesized Received in revised form phenylsulfonyl of benzothiazole and benzimidazole moiety-containing 14 December 2019 pyrazolo [5, 1-c]-l, 2, 4-triazine derivative [6, 7, 11.12, 16 and 17], Accepted 17 December 2019 arylhydrazone derivatives and pyridazine derivative [20, 21, 25, 26, 29 and 29] was carried out for antimicrobial and anticancer activity. The Keywords: synthesized compounds containing pyrazolo [5, 1-c]-l, 2, 4-triazine derivative Benzothiazoles [6, 7] exhibited higher activity against Staphylococcus aureus compared with Benzimidazoles control drug Chloramphenicol. While arylhydrazones 20 and 21 were found β-ketosulfones to be equal to the control drug. For antifungal activity, the compounds 6, 7, Pyrazolo[5,1-c]-l,2,4-triazine 20 and 21 were possessed the same potency as cycloheximide against Arylhydrazone Aspergillus fumigatus. The anticancer activity on Hepatocellular carcinoma Pyridazine (HEPG2) of the compounds 6, 7, 20 and 21 exhibited excellent activities, Antimicrobial more potent than the reference drug. The findings of this study are Anticancer worthwhile; however, further pharmaceutical and toxicological studies are recommended to be carried out. © 2020 The Authors. Published by IASE. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 1. Introduction derivatives possess important biological activities (Dai et al., 2013; Telvekar et al., 2012), anti-tumour *In recent decades, many outbreaks of (Weekes and Westwell, 2009), anticancer (Solomon antimicrobial resistance have been reported. This et al., 2009), antiproliferative agent (Racané et al., alarming phenomenon mainly results from the rapid 2018), anthelmintic and antiprotozoal (Mavrova et development of microbial mutation and resistance to al., 2010; Torres-Gómez et al., 2008), antibacterial drugs, while innovations in the pharmaceutical (He et al., 2004), antifungal (Göker et al., 2002), industry are very slow and disproportionate to this antiphrastic (Kopańska et al., 2004). β -keto sulfones growing risk, which requires new strategies to have attracted in synthetic chemists (Gopalan and control these mutant pathogens and launching Jacobs, 1990). The different pharmacological extensive investigations to develop new activities of heterocycles directed to synthesis antimicrobial drugs (Cheng et al., 2016; Cole, 2013). benzothiazole and benzimidazole derivatives (Ali et Similarly, the increasing recurrence of carcinoid al., 2016; Farag et al., 2008). The research program tumors worldwide with limited effective medications investigated synthesized β-ketosulphone shows the constant need to develop new anticancer benzimidazole and benzothiazole derivatives (1, 2) drugs (Ali et al., 2012). Benzothiazole and as an intermediate for the synthesis of new benzimidazole derivatives are notable heterocyclic derivatives (Darweesh et al., 2016). pharmacological activities heterocyclic compounds In continuation of a research program and an (Anand and Wakode, 2017; Váradi et al., 2014). Their attempt to develop new antimicrobial and anticancer drugs, the current study was carried out, which aimed to evaluate some biological properties * Corresponding Author. (antimicrobial and anticancer) of some synthesized Email Address: [email protected] (A. A. E. S. Abd Elaziz) heterocyclic derivatives containing pyrazoloazine https://doi.org/10.21833/ijaas.2020.02.010 Corresponding author's ORCID profile: and pyridazine incorporating benzothiazole and https://orcid.org/0000-0003-0525-6307 benzimidazole moieties. 2313-626X/© 2020 The Authors. Published by IASE. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) 69 Abd Elaziz et al/International Journal of Advanced and Applied Sciences, 7(2) 2020, Pages: 69-77 2. Materials and methods 133.43, 133.02, 136.22, 152.54, 156.04, 156.05, 156.63; MS (m/z): 394(M+) (100); IR (KBr): υ: 1607 2.1. Chemistry cm–1 (C=N). Anal. Found (calculated). For C17H10N6O2S2 (%): C, 51.73 (51.77); H, 2.57(2.56); S, All melting points were determined using an open 16.23 (16.26); N, 21.34 (21.31). glass capillary melting point apparatus. The infrared spectrophotometers using potassium bromide disks 4-(1-Methyl-1H-benzimidazol-2-yl)- method. The 1H and 13C NMR spectra were recorded 3(phenylsulfonyl)-[1, 2, 4]-triazolo[5, 1-c] [1, 2, 4]- on a Varian Mercury (VXR-300) NMR spectrometer triazine (12) at 300 and 75 MHz respectively using CDCl3 and DMSO-d6. Mass spectra were recorded on a Yield 72%; (mp. 110 ˚C); 1H NMR (300 MHz, Shimadzu GCMS-QP 1000 EX mass spectrometer at DMSO-d6): δ 4.02 (s, 3H, NCH3), δ 7.20-8.04 (m, 9H, 70 e.v. β -keto sulfones 1 and 2 (Darweesh et al., ArH’s), 8.47 (s, 1H, triazole-7-CH). 13C NMR (75 MHz, 2014), 3-(4-chlorophenyl)-5-amino-1H-pyrazole (3) DMSO-d6): δ 31.97, 111.67, 121.43, 123.60, 128.10, (Elnagdi et al., 1976), 2-cynomethylbenzothiazole 129.22, 133.36, 134.01, 136.02, 140.54, 141.11, (18) (Copeland and Day, 1943), diazonium salts of 5- 148.45, 148.57. MS (m/z): 391 (M+) (100); IR (KBr): amino-l,2,4-triazole (8) and 2-amino-1H- υ: 1607 cm–1 (C=N). Anal. Found (calculated). For benzimidazole (13) (Elnagdi et al., 1979) were been C18H13N7O2S (%): 55.19 (C, 55.23); H, 3.25 (3.35); S, ready by using methods from the literature. 8.21(8.19); N, 25.19 (25.05). 2.2. The reaction of β -keto sulfones 1 and 2 with 4-(Benzothiazol-2-yl)-3-(phenylsulfonyl)- [1, 2, 4] diazonium salt of heterocyclic amines 3, 8, 13 triazino [4, 3-a] benzimidazole (16) General procedure Yield 70%;( mp. 166 ˚C); 1H NMR (300 MHz, Dazonium salt of (5-amino-3- phenylpyrazole (3), DMSO-d6): δ 7.41-8.16 (m, 13H, ArH’s). MS (m/z): 3-amino-l, 2, 4-triazole (8), or 2-aminobenzimidazole 443 (M+) (100); IR (KBr): υ: 1607 cm–1 (C=N) Anal. (13) (2 mmol) was mixed to a stirred cold solution of Found (calculated). For C22H13N5O2S2 (%): C, 59.56 β -keto sulfones 1 and 2 (2 mmol) in pyridine (30 (59.58); H, 3.01 (2.95); S, 14.42 (14.46); N, 15.76 ml) for 30 min at 0-5ºC. The mixture was stirred for (15.79). 3 h after addition complete. The solid was obtained by filtration, washed thoroughly with H2O, dried. 4-(1-Methylbenzimidazol-2-yl)-3 (phenylsulfonyl)-1, Finally, recrystallization from DMF/H2O to afford 6, 2, 4-triazin- o[4, 3-a] benzimidazole (17) 7, 11, 12, 16 and 17, respectively. Yield 70%; (mp. 175 ˚C); 1H NMR (300 MHz, 2-(7-(4-Chlorophenyl)-3-(phenylsulfonyl) pyrazolo DMSO-d6): δ 4.02 (s, 3H, NCH3), δ 7.38-7.94 (m, 13H, [5, 1-c] [1, 2, 4]-triazin-4-yl) benzothiazole (6) ArH’s). MS (m/z): 440 (M+) (100); IR (KBr): υ: 1607 cm–1 (C=N). Anal. Found (calculated) For Yield 78%; (mp. 170˚C); 1H NMR (300 MHz, C23H16N6O2S (%): C, 62.68 (62.72); H, 3.64 (3.66); S, DMSO-d6): δ 7.42-8.13 (m, 13H, ArH’s), 6.99 (s, 1H, 7.33 (7.28); N, 19.12 (19.08). pyrazolo-8-CH). MS (m/z): 503.03 (M+) (100); IR (KBr): υ: 1597 cm–1 (C=N). Anal. Found (calculated). 2.3. The reaction of β -keto sulfones 1 and 2 with For C24H14N5ClO2S2 (%): C, 57.19 (57.20); H, 2.83 benzene diazonium chloride (2.80); S, 12.68 (12.72); N, 13.94 (13.90). Sodium acetate trihydrate (4 g). was added to a 7-(4-Chlorophenyl)-4-(1-methyl-1H-benzimidazol-2- stirred cold solution of keto-sulfone of benzothiazole yl)-3-(phenylsulfonyl) pyrazolo [5, 1-c]-1, 2, 4- 1 and benzimidazole 2 (10 mmol) in ethanol (25 ml), triazine (7) the mixture was cooled to 0°C and treated with aniline diazonium salt solution (10 mmol) with rapid Yield 72%; (mp. 188 ˚C); 1H NMR (300 MHz, stirring for 30 min and continued stirred for further DMSO-d6): δ 4.02 (s, 3H, NCH3), δ 7.20-7.89 (m, 13H, 2h at 0°C then stored at 4°C for 6 h. The mixture was ArH’s), 6.89 (s, 1H, pyrazolo-8-CH). MS (m/z): 500 filtrated to collect the solid product, washed with (M+) (100); IR (KBr): υ: 1597 cm–1 (C=N). Anal. water and dried; then recrystallized from ethanol to Found (calculated) For C25H17N6ClO2S (%): C, 59.96 yield arylhydrazone 20 and 21 respectively. (59.94); H, 3.39 (3.42); S, 6.41 (6.40); N, 16.80(16.78). 1-(benzothiazol-2-yl)-2-(2-phenylhyrazono)-2- (phenylsulfonyl) ethanone (20) 2-(3-(Phenysulfonyl) 1-[1, 2, 4] triazolo [5, 1-c][1, 2, 4]triazin-4-yl) benzothiazole (11) Yield 80%; (mp. 180 ˚C); 1H NMR (300 MHz, DMSO-d6): δ 7.07-8.33 (m, 14H, ArH’s) 11.11 (s, 1H, Yield 72%; (mp.