Prem M. S. Chauhan

Bio: Prem M. S. Chauhan is an academic researcher from Central Drug Research Institute. The author has contributed to research in topics: Antimalarial Agent & Indole test. The author has an hindex of 41, co-authored 156 publications receiving 4016 citations. Previous affiliations of Prem M. S. Chauhan include Academy of Scientific and Innovative Research & Indian Institute of Chemical Technology.

Present trends and future strategy in chemotherapy of malaria.

Abstract: This review starts from a brief introduction followed by the list of commercial antimalarial drug. According to the nature of chemical entities, these drugs have been divided into the following categories--Quinolines, pyrimidines, amidinies, guanidines, sulfonamides, sulfones, acridines, antibiotics and sesquiterpene lactones. The site of action and status of the antimalarial drugs have been described against each category. A brief description of reasons behind the search of a new antimalarial drug have been discussed. Finally, the review deals the well known biochemical target sites such as folate metabolism, pyrimidine metabolism and polyamines for the designing of antimalarial drugs. The detail description of the newly discovered biochemical target sites, alpha-tublin and DNA topoisomerases, have been highlighted. In the conclusion section, we have discussed the future strategies for the chemotherapy of malaria.

Cyanuric Chloride Catalyzed Mild Protocol for Synthesis of Biologically Active Dihydro/Spiro Quinazolinones and Quinazolinone-glycoconjugates

Abstract: We have developed an efficient cyanuric chloride (2,4,6-trichloro-1,3,5-triazine, TCT) catalyzed approach for the synthesis of 2,3-dihydroquinazolin-4(1H)-one (3a–3x), 2-spiroquinazolinone (5, 7), and glycoconjugates of 2,3-dihydroquinazolin-4(1H)-one (10a, 10b) derivatives. The reaction allows rapid cyclization (8–20 min) with 10 mol % cyanuric chloride to give skeletal complexity in good to excellent yield. We believe that this novel procedure may open the door for the easy generation of new and bioactive quinazolinones.

Discovery of a new class of natural product-inspired quinazolinone hybrid as potent antileishmanial agents.

Abstract: The high potential of quinazolinone containing natural products and their derivatives in medicinal chemistry led us to discover four novel series of 53 compounds of quinazolinone based on the concept of molecular hybridization. Most of the synthesized analogues exhibited potent leishmanicidal activity against intracellular amastigotes (IC50 from 0.65 ± 0.2 to 7.76 ± 2.1 μM) as compared to miltefosine (IC50 = 8.4 ± 2.1 μM) and nontoxic toward the J-774A.1 cell line and Vero cells. Moreover, activation of Th1 type and suppression of Th2 type immune responses and induction in nitric oxide generation proved that 8a and 8g induce murine macrophages to prevent survival of parasites. Compounds 8a and 8g exhibited significant in vivo inhibition of parasite 73.15 ± 12.69% and 80.93 ± 10.50% against Leishmania donovani /hamster model. Our results indicate that compounds 8a, 8g, and 9f represent a new structural lead for this serious and neglected disease.

I and i

Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

Marine indole alkaloids: potential new drug leads for the control of depression and anxiety

Abstract: The marine environment has been explored in the search for new bioactive compounds over the last 50 years, becoming a highly important and rich source of potent molecules and drug leads reported to possess a wide scope of activities. Alkaloids constitute one of the largest classes of natural products and are synthesized by terrestrial and marine organisms on all evolutionary levels. Alkaloids are usually present in an organism as a mixture consisting of several major and a few minor compounds of the same biosynthetic origin and differing only in functional groups. This group of compounds has apparently evolved as a defense mechanism against predators and as a result alkaloids are often highly potent and toxic molecules.1 Marine invertebrates have proven to be an outstanding source of active molecules, one of the most promising being indole alkaloids. Although many of these marine alkaloids closely resemble the endogenous amines (serotonin, dopamine or histamine), their potential affinity to various neurological targets and consequential impact on animal behavior is virtually unexplored. Indole alkaloids, their activity, synthesis and potential use in medicine have been already reviewed in several articles.2 In this review we provide information on current and potential pharmaceuticals including small molecule natural indole alkaloids, their biological properties, structure-activity relationship studies, and especially their potential for the treatment of neurological disorders. 1.1. The indole moiety in drugs The indole moiety is present in a number of drugs currently on the market. Most of these belong to triptans which are used mainly in the treatment of migraine headaches (Fig. 1). All members of this group are agonists of migraine associated 5HT1B and 5HT1D serotonin receptors. Sumatriptan (Imitrex) was developed by Glaxo for the treatment of migraines and introduced into the market as the first member of the triptan family.3 Relative to the second generation triptans, sumatriptan has lower oral bioavailability and a shorter half-life. Frovatriptan (FROVA®) was developed by Vernalis for the treatment of menstruation associated headaches. Frovatriptan's affinity for migraine specific serotonin receptors 5HT1B is believed to be the highest among all triptans.4 In addition, frovatriptan binds to 5HT1D and 5HT7 receptor subtypes.5 Zolmitriptan marketed by AstraZeneca is used to treat acute migraine attacks and cluster headaches. GlaxoSmithKline's naratriptan (Amerge) is also used in the treatment of migraines and some of its side effects include dizziness, tiredness, tingling of the hands and feet and dry mouth. All available triptans are well tolerated and effective.6 The highest incidence of central nervous system (CNS) related side effects (dizziness, drowsiness) was reported for zolmitriptan (5 mg), rizatriptan (10 mg) and eletriptan (40 mg, 80 mg).7 The differences in side-effect profiles for triptans are not likely caused by their different affinity towards serotonin receptors or other neurological receptors in the CNS. There is a positive correlation between the lipophilicity coefficient and CNS side effects; these undesired effects are also dose-dependent. Figure 1 Currently available drugs from the triptan group. 1.2. Serotonin receptors – possible targets for neurologically active marine indole alkaloids Given that depression affects approximately 18 million Americans annually,8 it is crucial to develop new effective treatments for this disorder. Intensive studies are being conducted in the area of new targets for antidepressant drugs,9,10 but most antidepressant drugs still target the neurotransmitter systems, mainly serotonin, dopamine and noradrenaline. Serotonin is one of the neurotransmitters present in the central and peripheral nervous system which plays an important role in normal brain function and regulates sleep, mood, appetite, sexual function, memory, anxiety and many others.11 Serotonin exerts its effects through seven families of receptors (5-HT1 – 5-HT7) further divided into several subclasses. Except for 5-HT3 receptor which is a ligand-gated ion channel, the serotonin receptors belong to the G-protein coupled receptor family. Due to a lack of selective ligands, there is still little known about several 5-HT receptor subclasses.12 Marine monoindole alkaloids, sharing structure similarities with serotonin, are certain to become useful tools to facilitate the understanding of serotonin receptor function and generate new drug leads for the treatment of depression, anxiety, migraines and other 5HT receptor related disorders.