Considerations concerning design and mechanism of action of a new class of anticancer dual DNA intercalators

Synthesis, structure, antimycobacterial and anticancer evaluation of new pyrrolo-phenanthroline derivatives

“…In the same time, benzo[c]phenanthridinium alkaloids as fagaronine and nitidine which showed antileukemic activity on rodents 44 and act as topoisomerase I and II inhibitors [45][46][47] , played the role of model compound for the development of new anticancer agents 14 . Having all these above consideration in mind and encouraged by our previous promising results in the field of anti-TB [25][26][27][28] and anticancer 29,30,32 derivatives with indolizine and/or phenanthroline skeleton, we have focused on the design of novel structures that contain four or five fused (hetero)cycles with pyrrolo[2,1-c] [4,7]phenanthroline skeleton (Scheme 3). In equal measure, we were interested to see the influence of the substituents at pyrrolo ring (especially the pharmacophoric moiety p-chloro-benzoyl 26 ) on the pharmacological properties, and if the increasing of number of fused rings from four to five will affect these properties (Scheme 3).…”

“…As part of our ongoing research in the field of design and synthesis of new anti-TB [25][26][27][28] and anticancer derivatives [29][30][31][32] with azaheterocycles skeleton, we report here the design, synthesis, structure and in vitro antimycobacterial and anticancer evaluation of new class of compounds with pyrrolo [2,1-c] [4,7]phenanthroline scaffold. To the best of our knowledge, there is no previous report, concerning the synthesis of pyrrolo [2,1-c] [4,7]-phenanthroline derivatives.…”

Hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives and evaluation of their anticancer and antimycobacterial activity

“…The structures of the new compounds were proven by elemental (C, H, N) and spectroscopic analysis: IR, 1 H NMR, 13 C NMR, and two-dimensional experiments 2D COSY, 2D HMQC, and 2D HMBC. If we consider compound 9 as representative for the first series of hybrid Imz (Bimz)/2-AP (8-AQ) derivatives 2,3,8,9 and 11c for the second series of hybrid N-(1-alkylcarboxy)-and N-allyl-Imz (Bimz)/2-AP (8-AQ) derivatives 5,6,10,11 , the spectral analysis reveals strong evidence for the proposed structures. Thus, in the case of compound 9, the most important signals furnished by 1 H NMR spectra are those one of the protons H9, H11, H13, H7, and H2.…”

“…One of the strategies widely used in cancer and TB therapy is targeting DNA with small molecules, imidazole/benzimidazole, and pyridine/quinoline derivatives being leading structures in this respect [anticancer [5][6][7][8][9][10] , anti-TB [11][12][13][14][15] ]. In previously research work, we successfully identify azaheterocycles derivatives (imidazole/benzimidazole and pyridine/quinoline included) with anticancer 9,10,[16][17][18][19] and anti-TB [15][16][17][20][21][22][23] activity.…”

“…3,4 It is well known from the literature [1][2][3][4] that imidazole (and its benzo-derivative benzimidazole) and pyridine (and its benzoderivative quinoline) derivatives are core scaffolds widely present in many classes of drugs (of natural or synthetic origin), displaying a large variety of interesting biological activities (antimicrobials, antifungus, anti-inflammatory, antihypertensive, antineuropathic, antihistaminic, etc. ; anticancer [5][6][7][8][9][10] and anti-TB 11-15 also included). Encouraged by the above considerations and in continuation of our research in the area of novel anticancer 9,10,[16][17][18][19] and anti-TB [15][16][17][20][21][22][23] derivatives with azaheterocyclic skeleton, we report here the design, synthesis, structure, and in vitro anticancer and antimycobacterial activity of new hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives.…”