Are we geared for the upcoming challenges by nCoV-19 or is it still grim news…?

The novel Corona Virus (nCoV-2019), clouded the entire world during the year 2020; with its emergence in December 2019 from Wuhan, China. The nCoV-19 is a novel variant of the Coronavirus family, with its predecessors been implicated for the pandemics of Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV); that caused flu-like condition and respiratory distress symptoms [1-6]. The viral strain also intrudes on extra-pulmonary relevance; being involved with deranging immunity as evidenced by lymphopenia and a prolonged prothrombin time; it impacts cardiomyocytes and pancreatic tissue directly [7-11]. These implications of nCoV-19 does suggest a long-term relevance of the disease profile. The emergenceof nCoV-2019 was quick to gain a pandemic status worldwide. An immense shift in the influx of the type of patients was observed, that imparted a false impression of a reduction in cardiovascular and metabolic patient presentation; formerly that had been the majority engaging the worlds’ healthcare facility. But as the world prepares itself for a possible second wave of the n-CoV-19, a prudent approach would be to remind us of the history lessons from the previous corona-led pandemic, such as MERS and SARS. This editorial will emphasize on channeling our focus to nCoV-19 implications on cardiovascular and metabolic disorders. The pandemics of SARS-CoV during 2002-2003 and MERS-CoV in 2012 highlight the long term relevance of coronavirus to cardiac and metabolic disease pathologies, both during and in the aftermath of these pandemics [3]. The SARS-CoV had demonstrated an increase of cardiovascular problems by 44%, hyperlipidemia by 68% and diabetes mellitus by 60%, in people who had recovered from the viral attack [12, 13]. Likewise, MERS-CoV had also embarked an increase of cardiac disorders by 30% and hypertension by 50% and diabetes mellitus by 50% [3, 8, 9]. Published research on nCoV-19 has hinted for a similar rising trend of cardiovascular and metabolic complexities. An increase in cardiac troponin level is observed with increased cases of myocarditis and heart failure [14]. A 20% increase in the incidence of diabetes and a 40 % rise in cardiovascular and cerebrovascular diseases is observed with nCoV-19 [8, 9]. Little do we comprehend that the involvement of angiotensin converting enzyme 2 (ACE2) receptors could play havoc on endothelium, kidney, intestine, liver and any other organ [15]. The nCoV-19 has thrown a curveball to the realm of the worldwide health and financial setting. Even with the current economic predicament it does seems prudent to be prepared in advance for the long term consequences of this pandemic. The bigger question would be to, not just direct our efforts at countering the possible second wave of nCoV-19 but also for the possible chaos of cardiovascular and metabolic disease outfall, impacting the world health system.

Phytochemical Studies of Lantana Camara Linn and Sturcture-Activity

The work embodied in the present thesis consists of two parts. Part A deals with the phytochemical studies on Lantana camara Linn., while part B describes the structure-activity relationship studies on some β-carboline alkaloids. A brief review of the biosynthesis of terpenoids with particular reference to the pentacyclic triterpenoids is also provided. PART A The introduction of Part A affords a review of the earlier contributions made in the chemistry and pharmacology of the genus Lantana and a brief account of the present work. Studies undertaken on the methanolic extract of the air dried aerial parts and roots of Lantana camara Linn. led to the isolation and structure elucidation of twenty four compounds including four new (17, 18, 21 and 23) and twenty known (1-16, 19, 20, 22 and 24) natural products. Compound 11 is hitherto unreported from aerial parts of the plant whereas compounds (4, 9 and 19) are reported for the first time from the genus Lantana. The constituents obtained in the present studies are listed below: Compounds obtained from aerial parts New Compounds 1. Lantanolide (17) 2. Lancamarolide (18) 3. Lancamarinic acid (21) 4. Lancamarinin (23) Known Compounds 5. Oleanonic acid (1) 6. b-Sitosterol (2) 7. Lantadene A (3) 8. 3-Oxo-11α-hydroxy-urs-12-ene-28-oic acid (4) 9. Oleanolic acid (5) 10. Ursolic acid (6) 11. Ursonic acid (7) 12. Betulinic acid (8) 13. 3β-Acetoxy Betulinic acid (9) 14. Lantadene B (10) 15. Pomonic acid (11) 16. Lantanilic acid (12) 17. Camaric acid (13) 18. Camarinic acid (14) 19. Lantaninilic acid (15) 20. Lantoic acid (16) 21. Stigmasterol (19) 22. Lantanolic acid (20) 23. Lantic acid (22) 24. β-Sitosterol-3-O-β-D-glucopyranoside (24) Compounds obtained from roots 1. Oleanonic acid (1) 2. Oleanolic acid (5) 3. Lantanilic acid (12) 4. β-Sitosterol-3-O-β-D-glucopyranoside (24) In the present investigation, the crude methanolic extract of the aerial parts of Lantana camara, its fractions and some pure compounds were evaluated for antileishmanial, nematicidal, mosquito larvicidal, anticancer and antioxidant activities. In addition, the extract and fractions were also evaluated for mosquito repellent, antibacterial, antifungal and insecticidal activities. Some pure compounds were also tested for immunomodulatory and enzyme inhibition activities. PART B The introduction of part B provides a review of the earlier contributions made in the chemistry and pharmacology of the β-carboline alkaloids – the harmine series of alkaloids. This part of the dissertation deals with the structure - activity relationship studies in the β-carboline alkaloids harmine (1), harmol (2) and harmalol (3) leading to the synthesis of thirty six derivatives (4-39) including eight new β-carbolines (20-25, 33 and 34) and five new tryptamine (35-39) derivatives along with several known compounds. Compounds 1 and 4-6 were tested for their leishmanicidal activity. Nematicidal activity of 2, 7, 8, 14-17 and 20-25 have also been determined. In addition compounds 2, 3 and 26-39 were tested for their antibacterial and antifungal activities. Some compounds were also investigated for their anticancer, chymotrypsin and urease inhibitory activities. The compounds synthesized in the present study are listed below: 1. 10-Bromo-11-methoxy-3-methyl-b-carboline (4) 2. 12-Bromo-11-methoxy-3-methyl-b-carboline (5) 3. 10,12-Dibromo-11-methoxy-3-methyl-b-carboline (6) 4. 10-Bromo-11-hydroxy-3-methyl-b-carboline (7) 5. 12-Bromo-11-hydroxy-3-methyl-b-carboline (8) 4 6. 11-Ethoxy-3-methyl-b-carboline (9) 7. 11-Butoxy-3-methyl-b-carboline (10) 8. 11-Isobutoxy-3-methyl-b-carboline (11) 9. 11-Pentoxy-3-methyl-b-carboline (12) 10. 11-Hexoxy-3-methyl-b-carboline (13) 11. 11-Heptoxy-3-methyl-b-carboline (14) 12. 11-Octoxy-3-methyl-b-carboline (15) 13. 11-Nonoxy-3-methyl-b-carboline (16) 14. 11-Decoxy-3-methyl-b-carboline (17) 15. 11-Allyloxy-3-methyl-b-carboline (18) 16. 11-Benzyloxy-3-methyl-b-carboline (19) 17. 11-2-Iodobenzyloxy-3-methyl-b-carboline (20) 18. 11-3-Iodobenzyloxy-3-methyl-b-carboline (21) 19. 11-4-Iodobenzyloxy-3-methyl-b-carboline (22) 20. 11-2-Nitrobenzyloxy-3-methyl-b-carboline (23) 21. 11-3-Nitrobenzyloxy-3-methyl-b-carboline (24) 22. 11-4-Nitrobenzyloxy-3-methyl-b-carboline (25) 23. 11-Acetoxy-3-methyl-b-carboline (26) 24. 11-Propionyloxy-3-methyl-b-carboline (27) 25. 11-Butyryloxy-3-methyl-b-carboline (28) 26. 11-Valeryloxy-3-methyl-b-carboline (29) 27. 11-Hexanoyloxy-3-methyl-b-carboline (30) 28. 11-Heptanoyloxy-3-methyl-b-carboline (31) 29. 11-Octanoyloxy-3-methyl-b-carboline (32) 5 30. 11-Nanoyloxy-3-methyl-b-carboline (33) 31. 11-Decanoyloxy-3-methyl-b-carboline (34) 32. 2-Acetyl-3-(2-nonanoylamidoethyl)-7-nonanoyloxyindole (35) 33. 2-Acetyl-3-(2-decanoylamidoethyl)-7-decanoyloxyindole (36) 34. 2-Acetyl-3-(2-trichloroacetamidoethyl)-7-trichloroacetoxyindole (37) 35. 2-Acetyl-3-[2-(2-trifloromethylbenzoyl)-amidoethyl]-7-(2- trifloromethyl benzoyloxy)-indole (38) 36. 2-Acetyl-3-[2-(3-trifloromethylbenzoyl)-amidoethyl)-7-(3- trifloromethyl benzoyloxy)-indole (39) Nematicidal activity was determined by Prof. Dr. Shaheena Fayyaz (Director) of the Institute of Nematological Research Center and Prof. Dr. Aly Khan (Director) of the Crop Disease Research Institute, Pakistan Agricultural Research Council, University of Karachi. Antimicrobial, antioxidant and immunomodulatory activities were tested by Prof. Dr. Aqeel Ahmed, Department of Microbiology, University of Karachi. Mosquito larvicidal and repellent activities were evaluated by Dr. M. Tariq Rajput, MAHQ Biological Research Centre, University of Karachi. Antileishmanial, anticancer, insecticidal and enzyme inhibition activities were determined by the bioassay screening section staff of this institute under the guidance of Prof. Dr. Muhammad Iqbal Choudhary. Extensive spectroscopic techniques such as UV, IR, EI-MS, HREI-MS, 1H- and 13C- NMR (Broad Band decoupled and DEPT), 2D NMR (1H-, 1H- COSY, NOESY, TOCSY, J-resolved, HMQC and HMBC) and chemical reactions were employed to elucidate the structures of the new compounds. The work embodied in the present dissertation has resulted in five research publications as listed in the list of publications.