Clinical Status of Anti-Cancer Agents Derived from Marine Sources

Abstract

The chemical, biological and ecological diversity of the marine ecosystem has contributed immensely in the discovery of extremely potent compounds that have shown potent activities in antitumor, analgesia, antiinflammatory, immunomodulation, allergy, anti-viral etc. The compounds of marine origin are diverse in structural class from simple linear peptides to complex macrocyclic polyethers. The recent advances in the sophisticated instruments for the isolation and characterization of marine natural products and development of high-throughput screening, have substantially increased the rate of discovery of various compounds of biomedical application. Didemnin was the first marine peptide that entered in human clinical trials in US for the treatment of cancer and other compounds such as dolastatin-10, soblidotin, didemnin B, ecteinascidin 743, girolline, aplidine, cryptophycins (also arenastatin A), bryostatin 1, ILX 651, kahalalide F, E7389, discodermolide, ES-285 (spisulosine), HTI-286 (hemiasterlin derivative), squalamine, KRN-7000, vitilevuamide, Laulimalide, Curacin A, diazonamide, peloruside A, eleutherobin, sarcodictyin, thiocoraline, salicylihalimides A, ascididemnin, CGX-1160, CGX-1007dictyodendrins, GTS-21 (aka DMBX), manoalide, IPL-576,092 (aka HMR-4011A) have entered in the clinical trials. This article summarize clinical status and synthetic advances of some of these compounds.

Antibody Drug Conjugates for Cancer Therapy

“…2), dolastatin 10 disrupts microtubules and kills cells with a potency 20-50 times greater than that of vinblastine (Bai et al, 1990). Several clinical trials investigating the antineoplastic activity of dolastatin 10, and a synthetic derivative TZT-1027, were performed but objective responses were not achieved (Singh et al, 2008a). Further derivatives of dolastain 10, containing substitutions at the C-terminal dolaphenine with norephedrine or phenylalanine, yielded auristatins E and F, respectively (Maderna et al, 2014).…”

Highlights of Natural Products in Prostate Cancer Drug Discovery

“…The preclinical pipeline continues to supply several hundred novel marine compounds every year and those continue to feed the clinical pipeline with potentially valuable compounds (Singh et al, 2008, Mayer et al, 2010. Thus, in the US there are three FDA approved marine-derived drugs, namely cytarabine (Cytosar-U ® , Depocyt ® , Fig.…”

Organismos marinhos como fonte de novos fármacos: histórico & perspectivas

“…57,103 Para os diversos kahalalidos (A-Q), outra série de depsipeptí-deos, já foram registradas suas atividades anticâncer, antimalarial, antipsoríase, tuberculostática, antifúngica e antiviral, mas foi apenas o kahalalido F (KF, Quadro 2) que apresentou significativa atividade contra linhagens de células tumorais humanas, inclusive pulmão e cólon, e contra alguns micro-organismos comumente oportunistas de pacientes portadores de HIV. [104][105][106] KF atua na membrana dos lisossomos, alterando sua função basal e induzindo a morte celular preferencialmente por oncose, 107-109 um Quadro 1 didemnina B: X = α-OH, H aplidina: X = O aplidin ® (aplidina, plitidepsina) Depsipeptídeo cíclico isolado da ascídia mediterrânea Aplidium albicans, com grande semelhança estrutural à didemnina B.…”