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Current Organic Synthesis

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ISSN (Print): 1570-1794
ISSN (Online): 1875-6271

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Research Article

Synthesis of Isatin Derivatives Exhibiting Antibacterial, Antifungal and Cytotoxic Activities

Author(s): Muhammad Saleem*, Maqbool Ahmad, Rana Farhat Mehmood, Afifa Shaheen, Shama Qaiser, Shah Iram Niaz, Muhammad Ali, Misbah Irshad, Sajid Mehmood, Samar A. Abubshait, Haya A. Abubshait, Muhammad Imran, Abdur Rauf, Omar M. Ali and Zeinhom M. El-Bahy

Volume 19, Issue 6, 2022

Published on: 29 April, 2022

Page: [748 - 756] Pages: 9

DOI: 10.2174/1570179419666220128091313

Price: $65

Abstract

Objective: The current objective was to synthesize biologically active Isatin derivatives. For this purpose, six (06) chemical entities of Isatin derivatives such as 3a-3c and 4a-4c were synthesized from Isatin substrate.

Methods: The pure compounds were characterized with the help of 1H-NMR, FT-IR, EIMS spectroscopic techniques. The synthesized amines 3a-3c and hydrazones 4a-4c were evaluated for their toxicity potential with the help of brine shrimp bioassay.

Results: The obtained results revealed that 3c exhibited promising toxicity (LD50 = 1.03 × 10-5 M) against Artemia salina. The pure chemical entities such as compounds 3a-3c and 4a-4c were evaluated against four Gram-negative (E. coli, P. aeruginosa, S. typhi, S. flexneri) and two Gram-positive (B. subtilis, S. aureus) bacteriae. The compound 3a displayed significant activity against two bacterial strains; i.e. P. aeruginosa, S. typhi, compound 3c demonstrated significant activity against P. aeruginosa. Compound 4b was the most active against S. typhi, displaying a greater diameter of the growth of inhibition zone (GIZ) than the standard drug. Compound 4c exhibited significant activity against P. aeruginosa and S. typhi. Compounds 3a-3c and 4a-4c exhibited moderate to significant antibacterial activity against three out of five strains. Only Compound 3c revealed promising toxicity (LD50 = 1.03 × 10-5 M) against Artemia salina. Antifungal studies of the compounds 3a-3c and 4a-4c against six fungal cultures; T. longifusus, C. albicans, A. flavus, M. canis, F. solani, and C. glabrata. All the compounds were active against one or more pathogens having inhibition (10- 90 %). Compound 3a exhibited significant inhibition i.e. 90 % against M. canis, 70 % against T. longifusus, compound 4b further displayed significant inhibition (90 %) against A. flavus and thus proved to be the most active member of the series.

Conclusion: All compounds showed better antibacterial, antifungal and cytotoxic activities, which may provide a ground to prepare enhanced molecules with much higher antibacterial activities.

Keywords: Isatin derivatives, cytotoxicity, antifungal activity, antibacterial activity, mass, FT-IR, 1HNMR, synthetic strategy.

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[1]
Rahim, F.; Taha, M.; Iqbal, N.; Hayat, S.; Qureshi, F.; Uddin, I.; Zaman, K.; Rab, A.; Wadood, A.; Uddin, N. Isatin based thiosemicarbazide derivatives as potential inhibitor of α-glucosidase, synthesis and their molecular docking study. J. Mol. Struct., 2020, 1222-128922.
[http://dx.doi.org/10.1016/j.molstruc.2020.128922]
[2]
Abbasi, I.; Nadeem, H.; Saeed, A.; Kharl, H.A.A.; Tahir, M.N.; Naseer, M.M. Isatin-hydrazide conjugates as potent α-amylase and α-glucosidase inhibitors: Synthesis, structure and invitro evaluations. Bioorg. Chem., 2021, 116, 105385.
[http://dx.doi.org/10.1016/j.bioorg.2021.105385] [PMID: 34600331]
[3]
Khatoon, S.; Aroosh, A.; Islam, A.; Kalsoom, S.; Ahmad, F.; Hameed, S.; Abbasi, S.W.; Yasinzai, M.; Naseer, M.M. Novel coumarin-isatin hybrids as potent antileishmanial agents: Synthesis, in silico and in vitro evaluations. Bioorg. Chem., 2021, 110, 104816.
[http://dx.doi.org/10.1016/j.bioorg.2021.104816] [PMID: 33799180]
[4]
Rasheed, S.; Ahmed, M.; Faisal, M.; Naseer, M.M. Isatin-3-thiosemicarbazone as Chromogenic Sensor for the Selective Detection of Fluoride Anion. Heterocycl. Commun., 2020, 26, 123-129.
[http://dx.doi.org/10.1515/hc-2020-0104]
[5]
Haider, A.; Ahmed, M.; Faisal, M.; Naseer, M.M. Isatin as simple, highly selective and sensitive colorimetric sensor for fluoride anion. Heterocycl. Commun., 2020, 26, 14-19.
[http://dx.doi.org/10.1515/hc-2020-0003]
[6]
Haider, A.; Ahmed, M.; Naseer, M.M. Highly Sensitive and Selective Naked Eye Detection of Fluoride anion with Isatin-thiazole Hybrid Molecule. Measurement, 2020, 154, 107457.
[http://dx.doi.org/10.1016/j.measurement.2019.107457]
[7]
Pervez, H.; Khan, N.; Iqbal, J.; Zaib, S.; Yaqub, M.; Naseer, M.M. Synthesis and in vitro bio-activity evaluation of N4-benzyl substituted 5-chloroisatin 3-thiosemicarbazones as urease and glycation inhibitors. Acta Chim. Slov., 2018, 65(1), 108-118.
[http://dx.doi.org/10.17344/acsi.2017.3649] [PMID: 29562103]
[8]
Pervez, H.; Khan, N.; Iqbal, J.; Zaib, S.; Yaqub, M.; Tahir, M.N.; Naseer, M.M. Synthesis, crystal structure, molecular docking studies and bio-evaluation of some N4-benzyl substituted isatin-3-thiosemicarbazones as antiurease and antiglycating agents. Heterocycl. Commun., 2018, 24, 51-58.
[http://dx.doi.org/10.1515/hc-2017-0148]
[9]
Hussain, M.; Bauzá, A.; Frontera, A.; Lo, K.M.; Naseer, M.M. Structure guided or structure guiding? Mixed carbon/hydrogen bonding in bis-Schiff base of N-allyl isatin. CrystEngComm, 2018, 20, 150-154.
[http://dx.doi.org/10.1039/C7CE01697B]
[10]
Doyle, A.A.; Stephens, J.C. A review of cinnamaldehyde and its derivatives as antibacterial agents. Fitoterapia, 2019, 139, 104405.
[http://dx.doi.org/10.1016/j.fitote.2019.104405] [PMID: 31707126]
[11]
Elancheran, R.; Kabilan, S.; Kotoky, J.; Ramanathan, M.; Bhattacharjee, A. In silico molecular docking, synthesis of 4-(4-benzoylaminophenoxy) phenol derivatives as androgen receptor antagonists. Combinator. Chem. High Through. Screen, 2019, 22(5), 307-316.
[http://dx.doi.org/10.2174/1386207322666190701124752]
[12]
Maruthanila, V.L.; Elancheran, R.; Roy, N.K.; Bhattacharya, A.; Kunnumakkara, A.B.; Kabilan, S.; Kotoky, J. In silico Molecular Modelling of Selected Natural Ligands and their Binding Features with Estrogen Receptor Alpha. Curr. Computeraided Drug Des., 2019, 15(1), 89-96.
[http://dx.doi.org/10.2174/1573409914666181008165356] [PMID: 30306879]
[13]
Elancheran, R.; Saravanan, K.; Divakar, S.; Kumari, S.; Maruthanila, V.L.; Kabilan, S.; Ramanathan, M.; Devi, R.; Kotoky, J. Design, Synthesis and Biological Evaluation of Novel 1, 3- thiazolidine-2, 4-diones as Anti-prostate Cancer Agents. Anticancer. Agents Med. Chem., 2017, 17(13), 1756-1768.
[http://dx.doi.org/10.2174/1871521409666170412121820] [PMID: 28403781]
[14]
Lashgari, N.; Ziarani, G.M. Synthesis of heterocyclic compounds based on isatin through 1, 3-dipolar cycloaddition reactions. J. Org. Chem., 2012, 1(1), 277-320.
[15]
Greenwell, M.; Rahman, P.K. Medicinal plants: their use in anticancer treatment. Int. J. Pharm. Sci. Res., 2015, 6(10), 4103-4112.
[PMID: 26594645]
[16]
Chemchem, M.; Menacer, R.; Merabet, N.; Bouridane, H.; Yahiaoui, S.; Moussaoui, S.; Belkhiri, L. Green synthesis, antibacterial evaluation and QSAR analysis of some isatin Schiff bases. J. Mol. Struct., 2020, 1208, 127853.
[http://dx.doi.org/10.1016/j.molstruc.2020.127853]
[17]
Azizian, J.; Mohammadi, K.M.; Firuzi, O.; Razzaghi-asl, N.; Miri, R. Synthesis, biological activity and docking study of some new isatin Schiff base derivatives. Med. Chem. Res., 2012, 21, 3730-3740.
[http://dx.doi.org/10.1007/s00044-011-9896-6]
[18]
Abo-Ashour, M.F.; Eldehna, W.M.; Nocentini, A.; Ibrahim, H.S.; Bua, S.; Abou-Seri, S.M.; Supuran, C.T. Novel hydrazido benzenesulfon-amides-isatin conjugates: Synthesis, carbonic anhydrase inhibitory activity and molecular modeling studies. Eur. J. Med. Chem., 2018, 157, 28-36.
[http://dx.doi.org/10.1016/j.ejmech.2018.07.054] [PMID: 30071407]
[19]
Liang, C.; Xia, J.; Lei, D.; Li, X.; Yao, Q.; Gao, J. Synthesis, in vitro and in vivo antitumor activity of symmetrical bis-Schiff base derivatives of isatin. Eur. J. Med. Chem., 2014, 74, 742-750.
[http://dx.doi.org/10.1016/j.ejmech.2013.04.040] [PMID: 24176732]
[20]
Sridhar, S.K.; Pandeya, S.N.; Stables, J.P.; Ramesh, A. Anticonvulsant activity of hydrazones, Schiff and Mannich bases of isatin deriva-tives. Eur. J. Pharm. Sci., 2002, 16(3), 129-132.
[http://dx.doi.org/10.1016/S0928-0987(02)00077-5] [PMID: 12128166]
[21]
Bal, T.R.; Anand, B.; Yogeeswari, P.; Sriram, D. Synthesis and evaluation of anti-HIV activity of isatin β-thiosemicarbazone derivatives. Bioorg. Med. Chem. Lett., 2005, 15(20), 4451-4455.
[http://dx.doi.org/10.1016/j.bmcl.2005.07.046] [PMID: 16115762]
[22]
Khan, K.; Mughal, M.; Ambreen, R.; Khan, N.; Perveen, A.; Choudhary, S.M. I Schiff bases of istain: Antiglycation activity. Lett. Drug Des. Discov., 2009, 6(5), 358-362.
[http://dx.doi.org/10.2174/1570180810906050358]
[23]
Raj, R.; Singh, P.; Singh, P.; Gut, J.; Rosenthal, P.J.; Kumar, V. Azide-alkyne cycloaddition en route to 1H-1,2,3-triazole-tethered 7-chloroquinoline-isatin chimeras: Synthesis and antimalarial evaluation. Eur. J. Med. Chem., 2013, 62(62), 590-596.
[http://dx.doi.org/10.1016/j.ejmech.2013.01.032] [PMID: 23434528]
[24]
Vine, K.; Matesic, L.; Locke, J.; Ranson, M.; Skropeta, D. Cytotoxic and anticancer activities of isatin and its derivatives: A comprehensive review from 2000-2008. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents) 2009, 9(4), 397-414.
[25]
Pervez, H.; Ahmad, M.; Yaqub, M.; Tahir, M.; Saira, N.N. -{2-[N-(4-Methylphenyl) oxamoyl] phenyl} propanamide. Acta Crystallogr. Sect. E Struct. Rep. Online, 2010, 66(7), 1729-1729.
[http://dx.doi.org/10.1107/S1600536810023263]
[26]
El-Faham, A.; Farooq, M.; Khattab, S.N.; Abutaha, N.; Wadaan, M.A.; Ghabbour, H.A.; Fun, H.K. Synthesis, characterization, and anti-cancer activity of some new N′-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones derivatives. Molecules, 2015, 20(8), 14638-14655.
[http://dx.doi.org/10.3390/molecules200814638] [PMID: 26287132]
[27]
Pervez, H.; Saira, N.; Iqbal, M.S.; Yaqub, M.; Khan, K.M. Synthesis and toxicity evaluation of some N4-aryl substituted 5-trifluoromethoxyisatin-3-thiosemicarbazones. Molecules, 2011, 16(8), 6408-6421.
[http://dx.doi.org/10.3390/molecules16086408] [PMID: 25134761]
[28]
Pervez, H.; Ahmad, M.; Yaqub, M.; Somra, M.; Iqbal, F.; Khan, K. Synthesis and biological evaluation of some novel isatins-derived hydrazones. J. Pharm. Res., 2011, 4(12), 4355-4358.
[29]
Carron, E.; Maran, J.; Montero, L.; Fernandozalgo, A.; Dominguez, A. Antimicrobial properties of some extracts obtained from some Mediterranean plants of medicinal value. Plantes Medicinales et Phytotherapie, 1987, 21, 195-202.
[30]
Choudhary, M.; Thomsen, I. Bioassay techniques for drug development; CRC Press, 2001.
[31]
Rauf, M.K.; Yaseen, S.; Badshah, A.; Zaib, S.; Arshad, R.; Imtiaz-Ud-Din, ; Tahir, M.N.; Iqbal, J. Synthesis, characterization and urease inhibition, in vitro anticancer and antileishmanial studies of Ni(II) complexes with N,N,N′-trisubstituted thioureas. Eur. J. Biochem., 2015, 20(3), 541-554.
[http://dx.doi.org/10.1007/s00775-015-1239-5] [PMID: 25604966]
[32]
Allen, C.; Drake, N.; Hamilton, C.S.; Shriner, R.; Smith, L.; Snyder, H. Organic Syntheses; Wiley: New York, 1955, 3, p. 456.

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