Table 2.

Small molecules showed antitumor activity in both adults and pediatric cancers. Reviewed in [229,230].

Ligand	Tumor model tested	Antitumor activity	Reference
Telomestatin	Neuroblastoma, myeloma, acute leukemia and glioma stem cells	Telomerase inhibition, telomere length reduction Inhibition of proto-oncogene c-Myb expression Antiprolifrative activity, apoptosis induction and increased chemosensitivity Impairs cancer stem cell survival and growth	[231,232,233,234,235,236,237,238,239,240]
S2T1-6OTD (telomestatin synthetic Derivative)	Paediatric brain cancer (Medulloblastoma and atypical teratoid/rhabdoid)	MYC and hTERT inhibition Telomere shortening Cell cycle arrest and tumor cell’s growth inhibition	[182]
HXDV (telomestatin syntheticDerivative)	A panel of normal/cancer telomerase- and ALT-positive cell lines	Inhibition of cell growth independently of telomerase activity M-phase cell cycle arrest Mitotic defects Induction of apoptosis	[241]
TMPyP4 (Cationic porphyrin)	Myeloma, cervical, pancreatic, breast, colon, prostate cancer and osteosarcoma, neuroblastoma and retinoblastoma	MYC and hTERT inhibition Blockage of telomerase elongation Antiproliferative activity	[242,243,244,245,246]
SYUIQ-5 and other quindoline derivatives	Leukemia, Burkitt’s lymphoma, human epithelial carcinoma, nasopharyngeal carcinoma	MYC and hTERT inhibition Antiproleferative activity cellular senescence; apoptosis induction	[2,41,58,226,247,248]
Tetrasubstituted napthalene diimides ligands	Brest, prostate cancer , and lung adenocarcinoma	Inhibition of telomerase, activity	[249]
Triazine derivatives	Melanoma, mouth, lung, colon cancer as well as, lung adenocarcinoma	Impairs the splicing machinery of hTERT by stabilizing quadruplexes located in the hTERT intron 6 Telomere shortening Antitelomerase activity, senescence and cancer cell growth arrest	[250,251,252,253,254]
Trisubstituted acridine (AS1410)	Breast and lung cancer	Synergistic activity in combination with cisplatin	[255]
BRACO-19 3,6,9-trisubstituted acridine	Breast and prostate cancer, uterus and vulval carcinoma	Decreases hTERT expression Induction of cellular senescence; cessation of cell growth	[252,253,256,257,258,259,260]
Pentacyclic acridines (RHPS4)	Melanoma, breast and vulval cancer	Telomerase inhibition Telomere capping disruption Apoptosis via PARP-1 activation Cell cycle perturbations and decrease in cancer cell growth Increased sensitivity to chemotherapy	[253,259,261,262,263,264,265,266]
4,5-di-substituted acridone	Breast and lung cancer	Inhibition of telomerase activity Telomere length shorting Senescence induction, cancer cell growth inhibition	[267]
Anthracene derivatives	Melanoma, colon cancer and osteogenic sarcoma	Telomere dysfunction Senescence and cell growth impairment	[268]
Amidoanthraquinone derivatives	60 different human cancer cell lines	Telomerase inhibition High anti-proliferative activity	[269]
Perylene derivatives	Melanoma, colon and breast carcinomas and osteosarcoma and colorectal carcinoma cell	Selectiv for telomeric G-quadruplex with respect to duplex genomic DNA. Telomerase inhibition.	[270,271]
Macrocyclic pyridyl polyoxazoles	Oral carcinoma and breast cancer	Selective for G-quadruplex DNA with no stabilization of duplex DNA or RNA Cytotoxic to cancer cell line	[272,273]
Triethylene tetramine (TETA)	Brest cancer and human epithelial carcinoma	Telomerase activity inhibition Induction of cellular senescence	[274,275]
Bisquinolinium pyridine dicarboxamide compound (360A)	Cervical cancer and colorectal carcinoma	Telomere aberrations Impair mitotic cell progression and lead to cell death.	[276,277]
307A 2,6-pyridin-dicarboxamide derivative	Glioma and osteosarcoma	Equipotent against MYC and telomeric G-quadruplex-forming sequences Inhibiting proliferation and induce apoptosis	[278]
Bisantrene derivatives (An1,5)	Melanoma and osteogenic sarcoma	Inhibit telomerase activity long-term cell growth inhibition in both telomerase- and ALT-positive cancer cell lines Induction of senescence and autophagy	[268]