SYNTHESIS AND UTILITY OF NEW POLYCYCLIC COMPOUNDS AS POTENTIAL ANTIMICROBIALS BASED ON CHROMENE MOIETY
Objective: The present research aims to synthesize some new polycyclic compounds including chromene moiety and study their antimicrobial activity.
Methods: Several new polycyclic systems including chromene scaffold incorporated with pyridine, pyrimidine, imidazopyrimidine, and imidazodiazocine were achieved via condensation reaction of chromene derivative under the proper condition with various reagents namely; cyanothioacetamide, phenyl isothiocyanate, malononitrile, carbon disulfide, benzaldehyde, triethylorthoformate, and 1,4-dichlorobutane. Moreover, a chlorodiazenyl chromene derivative was reacted with some substances possessing active–CH2-bridge such as ethyl cyanoacetate and malononitrile to end up with hydrazono compounds. Such compounds were eventually cyclized with hydrazine hydrate to form pyrazole and oxopyrazole derivatives. Moreover, compound 1 was treated with benzoyl acetone, and then followed by cyclization with malononitrile to provide the corresponding 2-amino14-(4-methoxyphenyl)-4-methy-5-phenyl-14H-benzo[5,6] chromeno[2,3H][1,6]naphthyridine-3-carbonitrile (20).
Results: The results of the antimicrobial screening in vitro revealed that the inhibition zone (mm) of the synthesized compounds 1-3, 5 and 8 implied their optimum antibacterial activity, while the compounds 4, 6 and 9-13, 15 showed a moderate to weak antibacterial activity against multiple species of B. subtilis, S. aureus, E. coli and P. aeruginosa. In contrast, the compounds 1, 6, 11, 15 showed high antifungal activities against different species of A. flavinand C. albicans, while the other compounds exhibit a moderate to poor antifungal activity.
Conclusion: It is remarkable that a series of chromene derivatives synthesized by a simple and available method leads to a molecule of promising antimicrobial activity. Further research is recommended to approve the importance of polycyclic systems for various applications.
2. Mwambete KD, Stephen WS. Antimicrobial resistance profiles of bacteria isolated from chicken droppings in Dar es Salaam. Int J Pharm Pharm Sci 2015;7:268-71.
3. Qingjing Y, Yanbo W, Shihui L, Jun (Joelle) W. Kinetic resolution and dynamic kinetic resolution of chromene by rhodium-catalyzed asymmetric hydroarylation. Angew ChemInt Ed 2019;58:5343-7.
4. Hassan Y, Sarg MT, El Deeb MA, Bayoumi AH, El Rabeb SI. Facile synthesis and anticancer activity study of a novel series of substituted and fused coumarin derivatives. J Heterocycl Chem 2018;55:1426-43.
5. Safari J, Heydarian M, Zarnegar Z. Synthesis of 2-amino-7-hydroxy-4H-chromene derivatives under ultrasound irradiation: a rapid procedure without catalyst. Arabian J Chem 2017;10:S2994–S3000.
6. Abd El-Wahab AHF. Synthesis, reactions and evaluation of the antimicrobial activity of some 4-(p-halophenyl)-4H-naphthopyran, pyranopyrimidine and pyranotriazolopyrimidine derivative. Pharmaceuticals (Basel) 2012;5:745-57.
7. Yanyang H, Rong H, Rongsheng T, Fengqiong L, Jianyou S, Mei Z. K2CO3¬ mediated synthesis of functionalized 4-substituted-2-amino-3-cyano-4H-chromenes via michael-cyclization reactions. Molecules 2014;19:19253-68.
8. Hai Feng G, Wei Wei C, Zheng F, Xin LST, Kai G. Efficient synthesis of chromenopyridine and chromene via MCRS. Chinese Chem Lett 2014;25:1357-62.
9. Jian X, Yuye C, Shuaizhu LW, Lubin XU, Hongtao W. Diversified construction of chromeno[3,4-c]pyridin-5-one and benzo[c]chromen-6-one derivatives by domino reaction of 4-alkynyl-2-oxo-2H-chromene-3-carbaldehyde. Adv Synth Catal 2014; 356:1835-45.
10. Isaac GS, Eugenia ML, Raguel PH. Enantioselective organocatalyzed synthesis of 2-amino-3-cyano-4H-chromene derivatives. Symmetry 2015;7:1519-35.
11. Srinivas T, Athira CK, Rajeev S. Facile synthesis of 4H-chromene derivatives via base mediated annulation of ortho-hydroxy chalcones and 2-bromoallyl sulfones. Beilstein J Org Chem 2016;12:16-21.
12. Lamia D, Mariem K, Noureddine A, Houcine A, Souhir A. Synthesis and antibacterial activity of 2-aminochromenes a rising cyanoiminocoumarins and ?-naphthol. Org Coumun 2017;10:32-9.
13. Deepali J, Anu M, Pratbha RMS, Bhartendu PT, Senehlata Y, Jaya S, et al. A visible light-initiated, on pot, multi-component synthesis of 2-amino-4-(5-hydroxy-3-methyl-1H-pyrazol-4-yl)-4-chromene-3-carbonitrile derivatives under solvent and catalyst-free conditions. Res ChemIntermed 2018;44:231-46.
14. Hu K, Lu A, Wang Y, Zhou Z, Tang C. Chiral bifunctionalsquaramide catalyzed asymmetric tandem michael-cyclization reaction; efficient synthesis of optically active 2-amino-4H-chromen-3-carbonitrile derivatives. Tetrahedron: Asymmetry 2013;24:953-7.
15. Vijay PP, Sunil UT, Balaji DR, Rajendra PP. Efficient and green synthesis of 2-amino-4H-chromenes. J Chem Pharm Res 2015;7:1057-61.
16. Kamdar NR, Haveliwala DD, Mistry PT, Patel SK. Desgin, synthesis and in vitro anti-mycobacterial activity of chromene fused cytosine and uracil analogues. Anti-infect Agents Med Chem 2013;1:41-7.
17. Chetanb SN, Shah MPP, Ranjang P. Microwave assisted synthesis of novel 4H-chromene derivatives bearing phenoxypyrazole and their antimicrobial activity assessment. J Serb Chem Soc 2012;77:1165-74.
18. El-Saghier AMM, Naili MB, Rammash Kh, Nabil AS, Khaled MK. Synthesis and antibacterial activities of some new fused chromenes. ARKIVOC 2007;16:83-91.
19. Nacy T, Subin MZ. Pharmacological activities of chromene derivatives and overview. Asian J Pharm Clin Res 2013;6:211-5.
20. Amol GJ, Suvidha SS, Dineshs P, Nagaiyan S. Phenylpyran-fused coumarin novel derivatives: a combined photophysical and theoretical study on the structural modification for PET-inhibited ICT emission. Struct Chem 2018;19:217-30.
21. Masesane IB, Desta ZY. Reaction of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives. Beilstein J Org Chem 2012;8:2166-75.
22. Bogza YP, Katsiel AL, Sharpova AN, Tolstikova TG, Fisyuk AS. Synthesis and biological activity of 4H-thieno[3,2-c] chromene derivative. Chem Heter Comp 2015;50:1712-8.
23. Okasha RM, Alblewi FF, Afifi TH, Naqvi A, Fouda AM, Al-Dies AM, et al. Design of new benzo[h]chromene derivatives: antitumor activities and structure-activity relationships of the 2,3-positions fused rings at the 2,3-positions. Molecules 2017;22:479-96.
24. El Azab IH, Mohamed MY, Mahmoud AA. Microwave-assisted synthesis of novel 2H-chromene derivatives bearing phenyl thiazolidinones and their biological activities assessment. Molecules 2014;19:19648-64.
25. Balalaie S, Bararjanian M, Sheikh Ahmadi M, Hekmat S, Salehi P. Diammonium hydrogen phosphate: an efficient and versatile catalyst for the one-pot synthesis of tetrahydrobenzo[b]pyran derivatives in aqueous media. Synth Commun 2007;37:1097–108.
26. Abbas S, Radineh M, Omidreza F, Savis M, Ahmad R, Ramin M. Synthesis and cytotoxic activity of novel benzopyrano [3,2-c]chromene-6,8-dione derivatives. Med Chem Res 2011;20:466-74.
27. Reddy RK, Rao SP, Dev JG, Poornachandra Y, Ganesh Kumar C, Rao SP, et al. Synthesis of novel 1,2,3-triazole/isoxazole functionalized 2H-chromene derivatives and their cytotoxic activity. Bioorg Med Chem Lett 2014;24:1661-3.
28. Chen JJ, Wang TY, Hwang TL. Neolignans. acoumarinolignan, lignan derivatives, and a chromene: anti-inflammatory constituents from Zanthoxylum avicennae. J Nat Prod 2008;71:212-7.
29. Fang JH, Yuan QS, Jing S, Jian BC, Hai JZ, Cai XY. Colorimetric detection of thiols using a chromenemolecule. Org Lett 2009;11:4918-21.
30. Mladenovic M, Vukovic N, Sukdolak S, Solujic S. Design of novel 4-hydroxy-chromene-2-one derivatives as antimicrobial agents. Molecules 2010;15:4294-308.
31. Serbetci T, Birteksoz S, Prado S, Michel S, Tillequin F. Synthesis and antimicrobial activities of some sulfur-containing chromene derivatives. Nat Prod Commun 2012;7:891-4.
32. Vukovic N, Sukdolak S, Solujic S, Niciforovic N. Substituted imino and amino derivatives of 4-hydroxycoumarins as a novel antioxidant, antibacterial and antifungal agents: synthesis and in vitro assessments. Food Chem 2010;120:1011-8.
33. Fadda AA, Berghot MA, Amer FA, Badawy DS, Bayoumy NM. Synthesis and antioxidant and antitumor activity of novel pyridine, chromene, thiophene and thiazole derivatives. Arch Pharm (Weinheim) 2012;345:378-85.
34. Mori J, Iwashima M, Takeuchi M, Saito H. A synthetic study on antiviral and antioxidativechromene derivative. Chem Pharm Bull 2006;54:391-6.
35. Naga Sudha B, Sridhara C, Girija Sastry C, Reddy YSR, Sreevidya O, Lavanya S, et al. Synthesis, characterization and anthelmintic activity of 3-(4-acetyl-5-phenyl-4,5-dihydro-1,3,4-oxadiazol-2-yl)-2H-chromen-2-one derivatives. Indian J Chem 2013;52B:422-7.
36. Bhavsar D, Trivedi J, Parekh S, Savant M, Thakrar S, Bavishi A, et al. Synthesis and in vitro anti-HIV activity of N-1,3-benzo[d]thiazol-2-yl-2-(2-oxo-2H-chromen-4-yl)acetamide derivatives using MTT method. Bioorg Med Chem Lett 2011;21:3443-6.
37. Cheng JF, Ishikawa A, Ono Y, Arrhenius T, Nadzan A. Novel chromene derivatives as TNF-alpha inhibitors. Bioorg Med Chem Lett 2003;3(13, Suppl 21):3647-50.
38. Sun W, Cama LD, Birzin ET, Warrier S, Locco L, Mosley R, et al. 6H-Benzo[c]chromen-6-one derivatives as selective ERbeta agonists. Bioorg Med Chem Lett 2006;16:1468-72.
39. Hussain MK, Ansari MI, Yadav N, Gupta PK, Gupta AK, Saxena R, et al. Design and synthesis of ER?/ER? selective coumarin and chromene derivatives as potential anti-breast cancer and anti-osteoporotic agents. RSC Adv 2014;4:8828-45.
40. Mungra DC, Patel MP, Rajani DP, Patel RG. Synthesis and identification of ?-aryloxyquinolines and their pyrano[3,2-c]chromene derivatives as a new class of antimicrobial and antituberculosis agents. Eur J Med Chem 2011;46:4192-200.
41. Vijaya KP, Rajeswar RV. Synthesis and antitubercular, antiviral and anticancer activity of 3-(3-mercaptoalkyl-7H-[1,2,4] triazolo[3,4-b][1,3,4]-thiadiazin-6-yl) chromen-2-one and its derivatives. Indian J Chem 2008;47B:106-11.
42. Bin L, Long Guan X, Xiao Hua X, Yong Hong L. Synthesis, crystal structure and herbicidal activity of 3-benzoyl-4-hydroxycoumarin derivatives. Chin J Org Chem 2011;31:2067-73.
43. Hegab MI, Abdulla MM. 4-Chloro-2, 2-disubstituted chromen-3-carboxaldehyde: synthesis of some fused polycyclic heterocycles as an anti-inflammatory, analgesic, anticonvulsant, and antiparkinsonian agents. Arch Pharm (Weinheim) 2006;339:41-7.
44. Ronad PM, Maddi VS, Koti BC, Kurhe YV, Swamy A, Swamy Ahmt, et al. Evaluation of the anticonvulsant activity of novel series of benzopyran-2-one derivatives by PTZ induced seizure model in mice. Indian J Novel Drug Delivery 2010;2:158-61.
45. Sivakumar KK, Rajasekaran A. Synthesis, in vivo analgesic and in vitro anti-microbial activity of 3-amino-4-[2-(substituted phenyl)hydrazin-1-ylidene]-1-[(2-oxo-2h-chromen-3-yl)carbonyl]-4, 5-dihydro-1hpyrazol-5-one and its schiff bases. Int J Res Pharm Chem 2014;4:517-27.
46. Hegab MI, Abdulla MM. 4-Chloro-2,2-disubstituted chromen-3-carboxaldehyde: synthesis of some fused polycyclic heterocycles as anti-inflammatory, analgesic, anticonvulsant, and antiparkinsonian agents. Arch Pharm (Weinheim) 2006;339:41-7.
47. Ronad PM, Maddi VS, Koti BC, Kurhe YV, Swamy A, Swamy Ahmt, et al. Evaluation of the anticonvulsant activity of novel series of benzopyran-2-one derivatives by PTZ induced seizure model in mice. Indian J Novel Drug Delivery 2010;2:158-61.
48. Patil RB, Sawant SD. Synthesis, docking studies and evaluation of antimicrobial and in vitro antiproliferative activity of 5H-chromene 4.3-d pyrimidine-2-amine derivatives. Int J Pharm Pharm Sci 2015;7:210-8.
49. Sawsan AF, Sadia AH, Samir YA, Amel MF, Yousry AA. Synthesis of hromen-2-one, yrano[3,4-c]chromene and yridino[3,4-c]chromeneerivatives as otentntimicrobial gents. Croat Chem Acta 2018;91:99-107.
50. Al-Majedy YK, Kadhum AH, Al-Amiery AA, Mohamad A. Coumarins: the antimicrobial agents. Sys Rev Pharm 2017;8:62-70.
51. Scott AC. Laboratory control of antimicrobial therapy. In: Collee JG. Eds. Practical Medical Microbiology. 13th edn. Edinburgh, Churchill Livingstone; 1989. p. 161–81.
52. Ramadan A, Mekheimer KUS. Microwave-assisted reactions: three-component process for the synthesis of 2-amino-2-chromenes under microwave heating. Chinese Chem Lett 2009;2:271-4.
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