Curcumin May Defy Medicinal Chemists

A recent review by Nelson et al.1 published in Journal of Medicinal Chemistry has concluded that curcumin does not satisfy any of the tenets of medicinal chemistry properties to qualify as a drug for any application. It has been pointed out that most of the results based on in vitro studies in cell lines are not reliable due to the interference in assay readouts, and in vivo and clinical study results are “much ado about nothing”. Curcumin is classified under PAINS (pans-assay interference compounds) and IMPs (invalid metabolic panaceas), and curcumin analogues for improved delivery systems are disregarded as “based on a fairly weak foundation”. A few other natural products listed under this category are ginsenosides, genistein, quercetin, apigenin, nordihydroguaiaretic acid, resveratrol, kaempferol, and fistein. With over 10,000 papers published and 120 clinical trials under various stages of progress using curcumin, the review is a huge dampener, considering the projected potential of curcumin and other natural products as a panacea. Even if 1% of the papers published make sense, it would still be a sizable number to warrant against passing a negative verdict on the whole field. The review has picked four clinical trials and concluded that given its low systemic bioavailability, it is doubtful whether oral curcumin would ever be effective in human clinical trials. It is also possible to pick examples where a significant beneficial effect is seen. In a randomized, registered, clinical trial with 45 rheumatoid arthritis patients, it was shown that curcumin formulation is superior to diclofenac sodium or even a combination in terms of a significant reduction in primary and secondary end points based on DAS (disease activity score) and ACR (American College of Rheumatology) criteria.2 In another registered trial with chronic obstructive pulmonary disease (COPD), mainly caused by smoking and leading to coronary artery disease, theracurcumin, a highly absorbable formulation of curcumin, was shown to cause a significant decrease in AT-LDL (α1-antitrypsin-low-density lipoprotein) in blood over placebo. The data obtained from 39 patients over a 6-month period warrants long-term study with cardiovascular events as primary end points.3 In terms of mechanisms involved, curcumin may act through mechanisms that are not addressed in the review.1 As an example, we would like to quote our studies on experimental malaria with P. berghei-infected mice. In a parasite recrudescence model created using suboptimal dose of arteether (single i.m. injection), the animals died