Sunday, August 1, 2021

Alkaloids : General Introduction, Occurrence /Distribution, Classification, Extraction and Chemical Test

 

What are Alkaloids?

·         Alkaloids are usually secondary metabolites.

·         The term alkaloid was coined by Meissner in 1819. Alkaloids are  “alkali like” substances / organic compounds.

·         They are basic nitrogen containing compound obtained from plant, animal and microorganism having marked physiological action.

·         They are basic in nature; they contain one or more nitrogen atom (usually in heterocyclic ring).

·         First synthesized alkaloid was connine.

Define the term Alkaloids.

Alkaloids are complex organic compounds of natural or synthetic origin which are basic in nature and contains one or more nitrogen atom, normally of heterocyclic nature and possess specific pharmacological activity on human or animal body, when used in small quantity.

Discuss the distribution of Alkaloids in the plant kingdom?

·         Rare in lower plants.

·         Dicots are richer in alkaloids than Monocots.

·         Families rich in Alkaloids: Apocynaceae, Rubiaceae, Solanaceae and Papaveraceae.

·         Families free from Alkaloids: Rosaceae, Labiatae.

·         They found in different parts of the plant:

ü  All Parts e.g. Datura

ü  Barks e.g. Cinchona

ü  Seeds e.g. Nux vomica

ü  Roots e.g. Aconite

ü  Fruits e.g. Black pepper

ü  Leaves e.g. Tobacco

ü  Latex e.g. Opium

Name the different forms in which alkaloids found in Plants.

  In the form of Free bases e.g. Caffeine

  Salts with Organic acids e.g. Oxalic, Acetic acid.

  Salts with inorganic acids e.g. HCl, H2SO4

  Salts with special acids: Meconic acid in Opiumin, Quinic acid in Cinchona.

  Glycosidal form e.g. Solanine in Solanum.

Discuss the role / functions of Alkaloids in Plants.

Alkaloids are doing following functions in the plants:

  They may act as protective against insects and herbivores due to their bitterness and toxicity.

  They are, in certain cases, the final products of detoxification (waste products).

  As a source of nitrogen in case of nitrogen deficiency.

  As a Carrier: For transportation of different acids.

  They, sometimes, act as growth regulators in certain metabolic systems.

  They may be utilized as a source of energy in case of deficiency in carbon dioxide assimilation.

Explain the various physical and chemical properties of the alkaloids.

1.      Physical Properties

A. Condition:

  Most alkaloids are crystalline solids.

  Few alkaloids are amorphous solids e.g. emetine.

  Some are liquids that are either:

ü  Volatile e.g. nicotine and coniine.

ü  Non-volatile e.g. pilocarpine and hyoscine.

B. Colour:

The majority of alkaloids are colorless but some are colored e.g.: Colchicine and berberine are yellow.

Canadine is orange.

C. Solubility:

  Both alkaloidal bases and their salts are soluble in alcohol.

  Generally, the bases are soluble in organic solvents and insoluble in water

Exceptions:

ü  Bases soluble in water: caffeine, ephedrine, codeine, colchicine, pilocarpine and quaternary ammonium bases.

ü  Bases insoluble or sparingly soluble in certain organic solvents: morphine in ether, theobromine and theophylline in benzene.

Salts are usually soluble in water and, insoluble or sparingly soluble in organic solvents.

Exceptions:

ü  Salts insoluble in water: Quinine monosulphate.

ü  Salts soluble in organic solvents: Lobeline and apoatropine hydrochlorides are soluble in chloroform.

 

2.      Chemical Properties

·         Alkaloids are basic in nature (Lone pair of electrons on nitrogen)

·         Basicity increased when adjacent functional group are electron releasing.

Primary amines R-NH2 e.g. Norephedrine

Secondary amines R2-NH e.g. Ephedrine

Tertiary amines R3-N e.g. Atropine

Quaternary ammonium salts R4-N e. g. d-Tubocurarine

·         Basicity order:  R2-NH > R-NH2 > R3-N

·         Saturated hexacyclic amines are more basic than aromatic amines.

·         Bases sensitive to decomposition whereas salts are stable.

Isomerisation:

  Optically active isomers may show different physiological activities.

  l-ephedrine is 3.5 times more active than d-ephedrine.

  l-ergotamine is 3-4 times more active than d-ergotamine.

  d- Tubocurarine is more active than the corresponding l- form.

  Quinine (l-form) is antimalarial and its d- isomer quinidine is antiarrhythmic.

   The racemic (optically inactive) dl-atropine is physiologically active.

Give the general classification of Alkaloids?

There are three main types of alkaloids: (1) true alkaloids, (2) protoalkaloids, and (3) pseudoalkaloids. True alkaloids and protoalkaloids are derived from amino acids, whereas pseudoalkaloids are not derived from these compounds.



A.   True Alkaloids

 

·         True alkaloids derive from amino acid and they contain a heterocyclic ring with nitrogen.

·         These alkaloids are highly reactive substances with biological activity even in low doses.

·         All true alkaloids have a bitter taste and appear as a white solid, with the exception of nicotine which has a brown liquid.

·         True alkaloids form water-soluble salts.

·         Moreover, most of them are well-defined crystalline substances which unite with acids to form salts. True alkaloids may occur in plants (1) in the free state, (2) as salts and (3) as N-oxides.

·         These alkaloids occur in a limited number of species and families, and are those compounds in which decarboxylated amino acids are condensed with a non-nitrogenous structural moiety.

·         The primary precursors of true alkaloids are such amino acids as L-ornithine, L-lysine, L-phenylalanine/L-tyrosine, L-tryptophan and L-histidine.

·         Examples of true alkaloids include such biologically active alkaloids as cocaine, quinine, dopamine and morphine.

 

B.    Proto-alkaloids / Amino Alkaloids

 

·         Proto-alkaloids are compounds, in which the N - atom derived from an amino acid and is not a part of the heterocyclic.

·         They are derived from L-tyrosine and L-tryptophan.

·         Proto-alkaloids are those with a closed ring, being perfect but structurally simple alkaloids.

·         Examples: Ephedra, Colchicum etc.

 

C.   Pseudoalkaloids

 

·         Pseudoalkaloids are compounds, the basic carbon skeletons of which are not derived from amino acids.

·         In reality, pseudoalkaloids are connected with amino acid pathways. They are derived from the precursors or post-cursors (derivatives the in-degradation process) of amino acids.

·         They can also result from the amination and transamination reactions of the different pathways connected with precursors or post-cursors of amino acids.

·         These alkaloids can also be derived from non-amino acid precursors.

·         The N atom is inserted into the molecule at a relatively late stage, for example, in the case of steroidal or terpenoid skeletons.

·         Examples of pseudoalkaloids include such compounds as coniine, capsaicin, ephedrine, solanidine, caffeine and theobromine.

 Give the Chemical classification of Alkaloids?

Alkaloids are mainly divided into two categories on the basis of their chemical structure, that is, heterocyclic rings.

 Atypical alkaloids

 These are also known as nonheterocyclic alkaloids and contain nitrogen in aliphatic chain.



Typical alkaloids

 These are also known as heterocyclic alkaloids and contain nitrogen in heterocyclic ring system.

 






For detailed classification and structure of basic nucleus refer: https://en.wikipedia.org/wiki/Alkaloid

Discuss the classification of Alkaloids based on biosynthetic origin.

Different metabolic pathways are involved in the biosynthesis of alkaloids. It is important to know precursor / starting material from which the alkaloids in question are produced in the plant biosynthetically. It is quite convenient and also logical to group together all alkaloids having been derived from the same precursor but possessing different taxonomic distribution and pharmacological activities.

Examples

(i) Indole alkaloids derived from tryptophan.

(ii) Piperidine alkaloids derived from lysine.

(iii) Pyrrolidine alkaloids derived from ornithine.

(iv) Phenylethylamine alkaloids derived from tyrosine.

(v) Imidazole alkaloids derived from histidine.

It is, however, pertinent to mention at this juncture that the enormous volume of authentic information accumulated so far with regard to the isolation of alkaloids from a variety of plant species and their subsequent characterization by the help of latest analytical techniques they may be classified as follows:

A. Alkaloids derived from Amination Reactions

(i) Acetate-derived Alkaloids

(ii) Phenylalanine-derived Alkaloids

(iii) Terpenoid Alkaloids

(iv) Steroidal Alkaloids

B. Alkaloids derived from Anthranilic Acid

(i) Quinazoline Alkaloids

(ii) Quinoline Alkaloids

(iii) Acridine Alkaloids

C. Alkaloids derived from Histidine

Imidazole Alkaloids

D. Alkaloids derived from Lysine

(i) Piperidine Alkaloids

(ii) Quinolizidine Alkaloids

(iii) Indolizidine Alkaloids

E. Alkaloids derived from Nicotinic Acid

Pyridine Alkaloids

F. Alkaloids derived from Ornithine

(i) Pyrrolidine Alkaloids

(ii) Tropane Alkaloids

(iii) Pyrrolizidine Alkaloids

G. Alkaloids derived from Tyrosine

(i) Phenylethylamine Alkaloids

(ii) Simple Tetrahydro iso-quinoline Alkaloids

(iii) Modified Benzyl Tetrahydro iso-quinoline Alkaloids

H. Alkaloids derived from Tryptophan

(i) Simple Indole Alkaloids

(ii) Simple b-Carboline Alkaloids

(iii) Terpenoid Indole Alkaloids

(iv) Quinoline Alkaloids

(v) Pyrroloindole Alkaloids

(vi) Ergot Alkaloids

 

Discuss the classification of Alkaloids based on their major pharmacological activity.

Interestingly, the alkaloids exhibit a broad range of very specific pharmacological characteristics. Perhaps this might also be used as a strong basis for the general classification of the wide-spectrum of alkaloids derived from the plant kingdom, such as: analgesics, cardio-vascular drugs, CNS-stimulants and depressants, dilation of pupil of eye, mydriatics, anticholinergics, sympathomimetics, antimalarials, purgatives, and the like. However, such a classification is not quite common and broadly known.

Examples

(iMorphine as Narcotic analgesic;

(iiQuinine as Antimalarial;

(iiiStrychnine as Reflex excitability;

(ivLobeline as Respiratory stimulant;

(vBoldine as Choleretics and laxatives;

(viAconitine as Neuralgia;

(viiPilocarpine as Antiglaucoma agent and miotic;

(viiiErgonovine as Oxytocic;

(ixEphedrine as Bronchodilator;

(xNarceine as Analgesic (narcotic) and antitussive.

 Explain the methods of extraction of Alkaloids from crude drug material.

The extraction of alkaloids is based on their basic character and solubility profiles. Generally, alkaloids are extracted mainly using two methods.

1.    Stass-Otto Method

  • The powdered material that contains alkaloidal salts is moistened with alkaline substances like sodium bicarbon-ate, ammonia, calcium hydroxide, etc., which combines with acids, tannins and other phenolic substances and sets free the alkaloids bases. 
  • Extraction is then carried out with organic solvents such as ether or petroleum spirit. 
  • The concentrated organic liquid is then shaken with aqueous acid and allowed to separate. 
  • Alkaloid salts will be present in aqueous liquid, while many impurities remain behind in the organic liquid.

 


Manskes Method

  • The collected powdered material is extracted with water or aqueous alcohol containing dilute acid. 
  • Chloroform or other organic solvents are added and shaken to remove the pigments and other unwanted materials. 
  • The free alkaloids are then precipitated by the addition of excess alkalis like, sodium bicarbonate or ammonia and separated by filtration or by extraction with organic solvents.



Volatile liquid alkaloids (nicotine and coniine) are isolated by distillation. The powdered material that contains alkaloids is extracted with water and the aqueous extract is made alkaline with sodium carbonate or ammonia and the alkaloid is distilled off in steam. This could be collected and purified.

 Discuss the general chemical tests used for the identification of Alkaloids.

The chemical tests are performed from neutral or slightly acidic solution of drug.

 Dragendorff’s Test

 Drug solution + Dragendroff’s reagent (Potassium Bismuth Iodide), formation of Orange- red colour.

 Mayer’s Test

 Drug solution + few drops of Mayer’s reagent (potassium mercuric iodide), formation of creamy-white precipitant.

 Hager’s Test

 Drug solution + few drops of Hagers reagent (Saturated aq. Solution of Picric acid), formation of crystalline yellow precipitate.

 Wagner’s Test

 Drug solution + few drops of Wagner’s reagent (dilute Iodine solution), formulation of reddish-brown precipitate.

 Tannic Acid Test

 Drug solution + few drops of tannic acid solution, formation of buff coloured precipitate.

 Ammonia Reineckate Test

 Drug solution + slightly acidified (HCl) saturated solution of ammonia reineckate, formation of pink flocculent precipitate.

 

 

 

 

 

 

 

 

 

Thursday, July 1, 2021

INTERNATIONAL JOURNAL OF MEDICAL, PHARMACEUTICAL AND BIOLOGICAL SCIENCES (IJMPBS) LAUNCHED ITS FIRST ISSUE


INTERNATIONAL JOURNAL OF MEDICAL, PHARMACEUTICAL AND BIOLOGICAL SCIENCES (IJMPBS)

International Journal of Medical, Pharmaceutical and Biological Sciences (IJMPBS) has launched today its first issue, April-June 2021. This issue comprises of total seven article which includes one editorial article written by the editor in chief. Anjali Pawar. The abstract of the other articles is summarized below:

1. Title: NANOFIBER AND CANCER - AN OVERVIEW OF RECENT DEVELOPMENTS

Authors: Iyer Aditya Manivannan, Syed Tazib Rahaman

Abstract: Cancer is a disease of grave concern. To combat the alarming need to provide an effective treatment methodology, Nanotechnology has become a powerful tool. It aids in achieving target-specific drug delivery to the tumour site. Nanofibers are among such nano-bio materials that can encapsulate antitumor drugs. In this review we tried to enlist various commercial nano-formulations, comprehend electrospinning as a means of developing nanofibers, brief on natural, semisynthetic and synthetic polymers such as Zein, Chitin, Chitosan, Poly-lactic acid, Poly lactic-co-glycolic acid, and Polycaprolactone suitable for nanofiber preparation, and applications of Nanofibers in delivery of a single drug as well as a combination of drugs or theranostic agents in cancer. It also describes three mechanisms of drug release from nanofibers, namely, pH-responsive, thermoresponsive and magnetic-heat composite release. The review tabulates the recent developments enlightening the applications of nanofibers in cancer chemotherapy in the past two decades. Nanofibrous mats are effective systems for localized treatment involving monotherapy, combination therapy, as well as for concomitant delivery of drugs and imaging agent, or genes. They have potential applications in the prevention of post-surgical cancer recurrence. Nanocomposite systems confer the ability to modulate drug release. Systems like nanoparticles which suffer from poor circulation time can be incorporated within nanofibrous mats. With many such unforeseen advantages and merits, Nanofiber becomes a potential nanotechnology driven system that enables patient-centric therapy for grave conditions like cancer. Read more

2. Title: MORPHOLOGICAL, PHYTOCHEMICAL AND PHARMACOLOGICAL ASPECTS OF SYZIGIUM CUMINI

Authors: Anjani M. Nikhare, Wrushali A. Panchale, Amar F. Sabhadinde, Jagdish V. Manwar, Ravindra L. Bakal

Abstract: Syzygium cumini, family Myrtaceae, a medicinal plant with numerous pharmacological activities such as anti-diabetic, antioxidant, anti-hyperlipidic and hepatoprotective. Seeds are moderately rich in protein and various phytochemicals along with flavonoids quercetin and, rutin a well-known antioxidant. Its leaves are used to treat leucorrhoea, stomachache, fever, dermopathy, constipation, inhibit blood discharge in feaces and reduce radiation induced DNA damage. Jamun fruit is an effective food remedy for bleeding piles and correcting liver disorders. This will help in confirmation of traditional use along with value-added utility of plant eventually leading to higher revenues from the plant. Read more

3. Title: DEVELOPMENT AND EVALUATION OF TASTE MASKED FORMULATIONS OF FEXOFENADINE HYDROCHLORIDE

Authors: Eshani Pradeep Rane,  Meghana Babar

Abstract: Ease of administration and patient compliance is gaining significant importance in the design of dosage forms. Dysphagia (difficulty in swallowing) is a common difficulty among all age groups especially in elderly and pediatrics. Patients suffering from dysphagia show greater chances of being choked during consumption of liquid formulation. Thus, to mollify such a problem, liquid formulation of high viscosity was prepared. The objective of present research work was to design and develop pediatric taste masked formulations of Fexofenadine hydrochloride (FEH) with taste enhancement and improved bioavailability. The masking of bitter taste of the drug was a necessity to formulate it in a palatable form. Effective taste masking of Fexofenadine hydrochloride was achieved through complexation with selected cyclodextrin (2- Hydroxypropyl beta cyclodextrin/ Cavasolw7HP). Inclusion complex prepared by solid dispersion showing taste score 1 (tasteless) was selected and further subjected to in-vitro taste assessment study. Based on human panel studies, tasteless FEH-2HPBCD complex i.e., batch FE5 was selected as optimized batch and different child friendly taste masking technologies were screened for incorporation of the same. Oral flavored powder formulations were prepared by mixing drug-2HPBCD inclusion complex equivalent to 30mg of FEH with varying concentrations of sucralose and with different flavors like chocolate, lemon, cherry, pineapple, etc. Formulation batch contaning lemon flavor F4 was more acceptable to human volunteers. Effervescent granules were formulated by using different concentration of effervescent salts, sucralose and lemon flavor. Soft chewable lozenges were formulated by optimization for binder concentrations and various flavors like chocolate, cherry, lemon, pineapple, etc. Results conclusively demonstrated that successful taste masking of FEH was accomplished and that it could be formulated for oral administration with more acceptability to pediatrics and improved bioavailability. Read more

4. Title: ORALLY DISINTEGRATING FILM: AN INNOVATIVE AND EASY APPROACH

Authors: Mohd Saif Mohd Akram Momin, Neha Inayat Hussain Ansari

Abstract: Orally disintegrating film (ODF) is a novel and simple method for delivering therapeutically or medicinally active chemical substances to the body(s). The major goals of orally disintegrating films (ODFs) are to improve drug’s bioavailability, permeability, and time to action, as well as enhance patient compliance. The process of making films is identical to that of making a transdermal patch. When a film is placed in the mouth, salivary fluid causes it to disintegrate quickly, releasing the medication(s). The medication(s) will subsequently be absorbed into the bloodstream, revealing therapeutic effect. This overview covers the pros and demerits of ODF formulations, as well as formulation aspects, technologies involved in making ODF formulations, and evaluation tests conducted for the same, as well as packing and storage. Orally disintegrating film formulations are a unique dosage form designed to enhance drug delivery, therapeutic action, and patient compliance. Read more

5. Title: COVID-19 VACCINES APPROVED FOR EMERGENCY USE AND UNDER DEVELOPMENT AROUND THE GLOBE – AN OVERVIEW

Authors: Harshal Ashok Pawar, Anjali Harshal Pawar, Sandip Ashok Pawar, Prashant Ashok Pawar

Abstract: COVID-19 has caused extensive human casualties with significant economic impacts around the globe, and has imposed new challenges on health systems worldwide. When the genetic sequence of SARS-CoV-2 was revealed, global vaccine companies and scientists have stepped forward to develop a vaccine, triggering a race toward vaccine development that the whole world is relying on.  Several vaccines against SARS-CoV-2, the virus that causes COVID-19, have been developed. The first vaccines available in the US (by Pfizer-BioNTech and Moderna) are messenger RNA (mRNA) vaccines. Another mRNA vaccine is available in Europe (CureVac). Other vaccines (by Janssen-Johnson & Johnson, Astra-Zeneca, Sputnik-V, and CanSino) are made using human and primate adenovirus vectors. A third type of vaccine available outside of the US is an inactivated whole-virus SARS-CoV-2 vaccine (by Bharat Biotech, Sinopharm and Sinovac). An effective and safe vaccine could play a pivotal role in eradicating COVID-19. However, few important questions regarding SARS-CoV-2 vaccine development are explored in this review. The present review gives an insight into the current status of vaccine development and associated outcomes reported at different phases of trial. Read more

6. Title: OVERTURE IN DEVELOPMENT, PROPERTIES AND CLINICAL ASPECTS OF BIOSURFACTANTS: AN REVIEW

Authors: Ashwini H. Bijewar, Wrushali A. Panchale, Jagdish V. Manwar, Ravindra L. Bakal

Abstract: Biosurfactants are a basically assorted gathering of surface-dynamic substances created by microorganisms. They are amphiphiles, they comprise of two sections- a polar (hydrophilic) moiety and non-polar (hydrophobic) congregation. In spite of a colossal measure of examination work over the most recent twenty years on conserving the creation of biosurfactants, their business accomplishment when contrasted with their manufactured partners actually stays a financial test. Utilization of immobilized organic entity, utilization of NPs, strong state aging, coordinated aging, froth fractionation, and fill and draw method of activity could end up being other promising cycles for the upgraded modern creation of different biosurfactants. Utilization of natural, fortified waste substrates and biosurfactants coproduction with another modern efficient item should be all the more basically concentrated particularly in huge aging vessels. In present work, we have covered various physicochemical and clinical aspects of biosurfactants. Read more

The current issue of the journal is available at : https://www.aphinfo.com/ijmpbs/current-issue




Aarya Publishing House introduced new journal entitled INTERNATIONAL JOURNAL OF MEDICAL, PHARMACEUTICAL AND BIOLOGICAL SCIENCES (IJMPBS)

Aarya Publishing House (APH) is a rapidly growing academic publisher with peer-reviewed, open access journals / books covering a wide range of academic disciplines. APH was established in the year 2013 with its registered office at Kalyan (Maharashtra), India. APH was established with clear cut goal of publishing quality and noteworthy publications. APH has introduced one more new journal entitled INTERNATIONAL JOURNAL OF MEDICAL, PHARMACEUTICAL AND BIOLOGICAL SCIENCES (IJMPBS).

INTERNATIONAL JOURNAL OF MEDICAL, PHARMACEUTICAL AND BIOLOGICAL SCIENCES (IJMPBS)


International Journal of Medical, Pharmaceutical and Biological Sciences (IJMPBS) is a peer reviewed online OPEN ACCESS journal . IJMPBS is intended primarily to promote rapid publication in the fields of Medicines, Pharmaceutical, and Biological Sciences. 

IJMPBS publishes original research work that contributes significantly to further the scientific knowledge in area of Medicine, Surgery, Pharmaceutics, Novel Drug Delivery, Biopharmaceutics, Pharmacokinetics, Nanotechnology, Pharmacognosy, Phytochemistry, Natural Product Research, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacology and Toxicology, Pharmaceutical Analysis, Quality Control, Quality Assurance, Drug Regulatory Affair, Pharmacy Practice, Clinical and Hospital Pharmacy, Pharmacogenomics, Bioinformatics, Pharmaceutical Biotechnology, Microbiology and other related fields. 

The Journal publishes original research work either as a Full Research Paper or as a Short Communication / Case study. Review Articles on a current topic in the said fields are also considered for publication by the Journal.

APH is planning to index IJMPBS with Scopus, Google Scholar, Chemical Abstract Services (CAS), Science Central, Index Copernicus, Pharmaceutical Science Open Access Resources (PSOAR), Rubriq, Directory of Research Journals Indexing, Journal Seeker, Directory of Science, Indian Science.in, Jour Informatics, China Knowledge Research Integrated (CNKI) database and other renowned electronic databases.

The editorial team of IJMPBS is founded by distinguished members of industry and academics from various disciplines and geopolitical region. The journal follows all the international regulatory requirements in order to ensure the quality of the articles and has bright future. The first issue of the journal is released today and it contains seven articles including editorial by the editor in Chief, Anjali Pawar. For more details refer : https://www.aphinfo.com/ijmpbs  (Source of the content).