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. 2020 Nov 26;10(70):42998-43009.
doi: 10.1039/d0ra08526j. eCollection 2020 Nov 23.

Synthesis of novel naphthalene-heterocycle hybrids with potent antitumor, anti-inflammatory and antituberculosis activities

Mohamed Ahmed Abozeid  1 , Aya Atef El-Sawi  1 , Mohamed Abdelmoteleb  2   3 , Hanem Awad  4 , Marwa Mostafa Abdel-Aziz  5 , Abdel-Rahman Hassan Abdel-Rahman  1 , El-Sayed Ibrahim El-Desoky  1
Affiliations

Synthesis of novel naphthalene-heterocycle hybrids with potent antitumor, anti-inflammatory and antituberculosis activities

Mohamed Ahmed Abozeid et al. RSC Adv. .

Abstract

Multitarget-directed drugs (hybrid drugs) constitute an efficient avenue for the treatment of multifactorial diseases. In this work, novel naphthalene hybrids with different heterocyclic scaffolds such as nicotinonitrile, pyran, pyranopyrazole, pyrazole, pyrazolopyridine, and azepine were efficiently synthesized via tandem reactions of 3-formyl-4H-benzo[h]chromen-4-one 1 with different nucleophilic reagents. Analysis of these hybrids using PASS online software indicated different predicted biological activities such as anticancer, antimicrobial, antiviral, antiprotozoal, anti-inflammatory, etc. By focusing on antitumor, anti-inflammatory, and antituberculosis activities, many compounds revealed remarkable activities. While 3c, 3e, and 3h were more potent than doxorubicin in the case of HepG-2 cell lines, 3a-e, 3i, 6, 8, 10, 11, and 12b were more potent in the case of MCF-7. Moreover, compounds 3c, 3h, 8, 10, 3d, and 12b manifested superior activity and COX-2 selectivity to the reference anti-inflammatory Celecoxib. Regarding antituberculosis activity, 3c, 3d, and 3i were found to be the most promising with MIC less than 1 μg mL-1. The molecular docking studies showed strong polar and hydrophobic interactions with the novel naphthalene-heterocycle hybrids that were compatible with experimental evaluations to a great extent.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1. Representative examples for naphthalene containing marketed drugs.
Fig. 2
Fig. 2. Design of new naphthalene hybrid skeletons.
Scheme 1
Scheme 1. Reaction of formylchromone 1 with cyanoacetanilides 2a–h.
Scheme 2
Scheme 2. Reaction of formylchromone 1 with cyanoacetic acid hydrazide.
Scheme 3
Scheme 3. Reaction of formylchromone 1 with thiosemicarbazide and o-aminothiophenol.
Scheme 4
Scheme 4. Reaction of formylchromone 1 with hydrazine hydrate.
Scheme 5
Scheme 5. Reaction of formylchromone 1 with 4-aminoantipyrine and 2-aminobenzothiazole.
Fig. 3
Fig. 3. Dose-dependent cytotoxic activities for the synthesized compounds on HepG-2.
Fig. 4
Fig. 4. Dose dependent cytotoxic activities for the synthesized compounds on MCF-7.
Fig. 5
Fig. 5. Binding modes (A) 3c and 2I4I; (B) 3e and 2I4I; (C) 3h and 2I4I; (D) 3c and 5GWK; (E) 3e and 5GWK; (F) 3h and 5GWK.
Fig. 6
Fig. 6. Binding modes (A) 3c and COX-2 (PDB 4PH9); (B) 3h and COX-2 (PDB 4PH9).
Fig. 7
Fig. 7. Binding of 3c with M. tuberculosis InhA (PDB 4DRE).
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References

    1. Makar S. Saha T. Singh S. K. Eur. J. Med. Chem. 2019;161:252–276. doi: 10.1016/j.ejmech.2018.10.018. - DOI - PubMed
    1. El-Desoky S. I. Keshk E. M. El-Sawi A. A. Abozeid M. A. Abouzeid L. A. Abdel-Rahman A. H. Saudi Pharm. J. 2018;26:852–859. doi: 10.1016/j.jsps.2018.03.013. - DOI - PMC - PubMed
    2. Abozeid M. A. El-Kholany M. R. Abdel-Rahman A. H. El-Desoky S. I. Int. J. Mod. Org. Chem. 2018;5:1–11.
    3. Abozeid M. A. El-Kholany M. R. Abouzeid L. A. Abdel-Rahman A. H. El-Desoky S. I. J. Heterocycl. Chem. 2019;56:2922–2933. doi: 10.1002/jhet.3686. - DOI
    4. El-Desoky S. I. El-Sawi A. A. Abozeid M. A. Abdelmoteleb M. Shaaban M. Keshk E. M. Abdel-Rahman A. H. Med. Chem. Res. 2019;28:1601–1617. doi: 10.1007/s00044-019-02397-3. - DOI
    5. Abozeid M. A. El-Sawi A. A. Elmorsy M. R. Abdelmoteleb M. Abdel-Rahman A. H. El-Desoky S. I. RSC Adv. 2019;9:27996–28005. doi: 10.1039/C9RA05154F. - DOI - PMC - PubMed
    1. Valente S. Trisciuoglio D. De Luca T. Nebbioso A. Labella D. Lenoci A. Bigogno C. Dondio G. Miceli M. Brosch G. J. Med. Chem. 2014;57:6259–6265. doi: 10.1021/jm500303u. - DOI - PubMed
    2. Abate C. Niso M. Lacivita E. Mosier P. D. Toscano A. Perrone R. J. Med. Chem. 2011;54:1022–1032. doi: 10.1021/jm1013133. - DOI - PubMed
    1. Perrone R. Doria F. Butovskaya E. Frasson I. Botti S. Scalabrin M. Lago S. Grande V. Nadai M. Freccero M. Richter S. N. J. Med. Chem. 2015;58:9639–9652. doi: 10.1021/acs.jmedchem.5b01283. - DOI - PMC - PubMed
    1. Özdemir Z. Sari S. Karakurt A. Dalkara S. Drug Dev. Res. 2019;80:269–280. doi: 10.1002/ddr.21491. - DOI - PubMed